7189 results for "canc*"

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• Spatial Transcriptomics Uncovers Tumor Microenvironment-Based Subtypes in Invasive Lobular Carcinoma

  Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer (BC); however, little is known about its tumor microenvironment (TME). Here, we investigated the spatial architecture of 43 hormone-receptor-positive, HER2-negative (HR+/HER2-) primary ILC samples, using spatial transcriptomics and detailed morphological annotation. By integrating morphology, spatial, and single-cell data, we mapped TME-related cell types, exploring their proximity to tumor cells and their enrichment in specific compartments. Clustering of spatial transcriptomics spots revealed significant inter- and intra-tumor heterogeneity, identifying pathways and cell types linked with disease outcomes. Morphological and gene expression data were finally integrated with a multimodal approach, leading to the identification of 4 new ILC subtypes based on TME heterogeneity. By using derived, specific gene expression signatures, these subtypes were identified and validated in external bulk RNA-seq/microarray datasets (SCAN-B and METABRIC), where differences in prognosis emerged.

  Study EGAS50000001001

• ST lobular manuscript dataset

  Spatial transcriptomics analysis for 43 breast cancer lobular samples. Note that there are 2 runs per sample Images and read counts will be made availalble on Zenodo upon publication.

  Dataset EGAD50000001467

• PD1-targeted delivery of an IL-2 variant induces a multifaceted anti-tumoral T cell response in human lung cancer

  To explore PD1-IL2v-specific effects on CD8 and CD4 T cells at a transcriptomic level, we performed single-cell RNA sequencing of patient-derived tumor fragments (PDTFs) which were treated with either Isotype (DP47), Isotype-IL2v (DP47-IL2v), anti-PD1 (PembroPGLALA) or PD1-IL2v (PembroPGLALA-IL2v) for 48 hours.

  Study EGAS50000000396

• p200503_fn2

  RNA-Sequencing data of Fusobacterium nucleatum (Fna 71) treated CRC patient derived (CAF180, CAF181) and CAF05 cancer associated fibroblasts (CAFs).

  Study EGAS50000001121

• RNA-Sequencing data of Fusobacterium nucleatum treated CAFs and HT-29 tumor spheroid exposed to Fusobacterium nucleatum treated CAFs conditioned medium.

  RNA-Sequencing data of CAFs (patient derived CAF180 and CAF181 as well as the CT5.3 CAF cell line) and HT-29 tumor spheroid samples performed in the context of the study of the interaction of Fusobacterium nucleatum with CRC CAFs. Fusobacterium nucleatum interacts with cancer-associated fibroblasts to enhance colorectal cancer progression

  Dataset EGAD50000001614

• Batches 1-3 prostatectomy analysis

  Whole Genome Sequencing Illumina HiSeq data from 95 men with prostate cancer. Samples were taken from primary tissue obtained at prostatectomy (target sequencing depth 50X) with matched blood control (target sequencing depth 30X). This data is from batches 1 to 3 and is the bulk of the data used in Wedge et al, Nature Genetics 2018 (PMID: 29662167). As of September 2020, some of the studies using these data include: Wedge et al, Nature Genetics 2018 (PMID: 29662167) Pan-Cancer Analysis of Whole Genomes, Nature 2020 (PMID: 32025007)

  Dataset EGAD00001001116

• The Oral Microbiome and Head and Neck Cancer

  Oral microbiota may influence head and neck squamous cell carcinoma (HNSCC) development, potentially related to carcinogen metabolism. The human oral cavity hosts a diverse microbiota, including bacteria and fungi. We performed shotgun sequencing and ITS1 sequencing on 236 HNSCC case participants who developed HNSCC during a mean follow-up of 5.1 years and 458 matched controls who remained HNSCC-free. Oral samples were obtained from a prospective nested case-control study within three epidemiological cohorts: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (ACS CPS-II), the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the Southern Community Cohort Study (SCCS). Control participants were selected using 2:1 frequency matching based on cohort, age, sex, race and ethnicity, and time since oral sample collection.

  Study phs004018

• Oncogenome of Kaposi Sarcoma

  Kaposi Sarcoma (KS) is an aggressive cancer caused by the Kaposi Sarcoma Herpesvirus (KSHV/HHV-8). Individuals with immunodeficiencies, exemplified by HIV, have an elevated risk of developing KS. However, understanding of the genetic factors contributing to KS progression is still limited. To explore potential genetic alterations in KS that could offer biological or therapeutic insights, whole exome sequencing was performed on 78 KS tumors and matching normal skin samples from 59 adults with KS (46 with HIV-associated KS and 13 with HIV-negative KS) receiving treatment at the Uganda Cancer Institute in Kampala, Uganda. Results showed a very low mutational burden in all samples except one (median = 11 mutations), which is the smallest number of mutations found across all 33 cancer types in The Cancer Genome Atlas (TCGA). No recurrent mutations were identified. Mutational signatures included impaired DNA mismatch repair and smoking. There was no evidence suggesting that multiple tumors from the same patient originated from a single clone. The number of genome copy alterations per genome was higher in tumors from individuals without HIV and those with advanced-stage disease. This suggests that lesions that take longer to develop may accumulate more alterations, although the overall number of alterations remains low compared to other cancers. These findings suggest that KS pathogenesis differs from other cancers, with KSHV viral infection and the expression of viral oncogenes being the primary drivers of carcinogenesis, rather than clonal oncogenic transformation arising from genetic alterations of cancer-related cellular genes.

  Study phs003897

• PE-CGS: Optimizing Engagement of Hispanic Colorectal Cancer Patients in Cancer Genomic Characterization Studies

  Colorectal Cancer (CRC) is the second leading cause of cancer death in the US. Hispanic/Latinos (H/L) are the largest and fasting growing ethnic group in the US, and cancer is the leading cause of death among H/L in the US. Therefore, we need to fully understand the full complexity of the molecular etiology of cancer in this ethnic group. For instance, although incidence rates of CRC are lower among Latinos as compared to Whites or African Americans, Hispanics with metastatic disease have shorter overall survival when adjusted for health care setting, demographics, disease characteristics and treatment factors. H/L also tend to be diagnosed at a younger age and with higher stage, and we have previously reported that Mexican H/L in California have the greatest proportion of young (The Cancer Genome Atlas has provided a deep overview of the molecular taxonomy of CRC in 594 cases, however, less than 1% of the cases (n=5) were H/L. Therefore, it is imperative for us to take more detailed assessment of the molecular genomic landscape of CRC in H/L. One of the major issues likely limiting our ability to perform these large genomic initiatives in minority patients is that Patient or Participant Engagement practices may not be investigated to identify best practices for accruing and consenting patients into clinical translational biomedical research studies. This concept of Participant Engagement is critically important for both the patients and the translational cancer research community. Optimizing and improving our approaches for directly engaging patients at initial contact, throughout the course of a translational genomic study, and during the time of return of results is likely to lead to stronger relationships between the medical community and patients, but could also lead to significant improvement in outcomes for patients and for the cancer care community as a whole. As such, we propose the creation of the USC Center for Optimization of Participant Engagement in Cancer Characterization (COPECC) with a focus on optimizing the engagement of Latinos in CRC Genomic Characterization research studies. USC COPECC would serve as a member of the NCI U2C Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Our investigative team includes experts in all relevant areas of research for genomic characterization, participant engagement, and engagement optimization. We have an established platform for consenting patients into cancer genomics studies that will serve as a standard process. The overall goal of USC COPECC is to generate results on participant engagement optimization and CRC genomic research that will be shared with the broader community to distribute best practices for engaging Latinos in hopes of improving overall outcomes for CRC in this underserved population.

  Study phs003985

• Collagen XVII Promotes Pancreatic Cancer Through Regulation of PIK3R5

  Pancreatic ductal adenocarcinoma (PDAC) contains a desmoplastic stroma that promotes the aggressive biology of this disease. While the varied mechanisms by which fibrillar collagens contribute to PDAC have been defined, little is known about the contribution of transmembrane collagens. Among this class of collagens, Collagen XVII uniquely contains an extensive intracellular domain that connects intracellular cytoplasmic components with the extracellular matrix. Collagen XVII is best characterized as the defining component of the type I hemidesmosome, an anchoring complex that attaches epithelial cells to the underlying basement membrane. In this study, we characterize the expression of collagen XVII in PDAC and the mechanisms by which it contributes to PDAC biology. We demonstrate that crosstalk between PDAC cells and cancer associated fibroblasts drive collagen XVII expression in vitro and xenograft tumor models in vivo. Genetic depletion of collagen XVII in low-passage patient derived cell lines diminishes their metastatic potential and ability to form tumors in mice. Whole transcriptome sequencing of tumors formed by cells with diminished collagen XVII levels revealed dramatically lower levels of PIK3R5, a regulatory subunit of class IB phosphatidylinositol-3-kinase (PI3K) that interacts with G protein-coupled receptors. Consistent with this, collagen XVII-deficient tumors exhibited lower levels of phosphorylated AKT, a downstream effector of PI3K. The studies highlight the importance of collagen XVII signaling in PDAC and define a novel mechanism by which collagen XVII mediates activation of PI3K.

  Study phs003641

• KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia

  NUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML). NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. Here we show that MYST family histone acetyltransferase (HAT) complex proteins including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1 associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of Kat6a and Kat7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r AML.

  Study EGAS50000001075

• Multi-omics analysis of an individual with multiple pancreatic neuroendocrine tumours (panNETs)

  Study EGAS00001006722

• Dataset with WGBS data of CRC and colon tissue

  This dataset contains WGBS data from 20 samples, which are either from colorectal cancer or control colon tissue. Sequencing was performed on either Illumina HiSeq 2000 or HiSeq X and the sequences are paired.

  Dataset EGAD50000000772

• Whole-genome and transcriptome versus panel sequencing in precision oncology: A translational-clinical comparison

  Precision oncology offers new cancer treatment options. While the use of whole-genome (WGS) and transcriptome (TS) sequencing remains often confined to specific clinical programs, molecular analysis with gene panels is more common clinical practice. Methods: Twenty patients with rare or advanced tumors sequenced by WGS/TS within the DKFZ/NCT/DKTK-MASTER program from 2015 to 2020 (MASTER 1) were additionally sequenced with the TSO500 DNA and TST170 RNA Assay by Illumina. Original Molecular Tumor Board (MTB) therapy recommendations (TR) were juxtaposed with TR from NGS panel data analysis (comparison 1). To mitigate temporal differences between the two sequencings, WGS/TS was bioinformatically reanalyzed (MASTER 2), and new TR were again compared (comparison 2). Results: In comparison 1, 47.1% of the MASTER 1’s TR and 62.8% of the panel’s TR were identical, as were 45.9% of the TR of MASTER 2 and 54.9% of the panel in comparison 2. In both MASTER 1 and MASTER 2, 26.5% and 36.1% of TR, respectively, relied on Biomarkers (BM) which were not covered by the panel. Eight of the ten MTB-derived therapy implementations were also supported in the panel, the two remaining ones being based on BM absent from the panel. Conclusions: About half of the TR in WGS/TS and panel sequencing were identical. Around a third of TR issued by WGS/TS were based on BM which are not covered by the panel, leading to therapy implementations. The presented data underscores the clinical value of comprehensive molecular analyses in individuals with advanced cancers.

  Study EGAS50000000431

• High-grade B-cell lymphoma, not otherwise specified: an LLMPP study

  Molecular characterization of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is hindered by its rarity, evolving definition, and poor diagnostic reproducibility. To address this challenge, we analyzed 92 HGBCL-NOS tumors collected across Lymphoma/Leukemia Molecular Profiling Project sites. These tumors were profiled using whole-genome sequencing (WGS) or whole-exome sequencing (WES) to identify somatic mutations, WGS or low-pass WGS to detect copy number alterations, targeted capture sequencing to assess MYC and BCL2 structural variants, and RNA sequencing. The genetic features of HGBCL-NOS were compared to those of diffuse large B-cell lymphoma (DLBCL-NOS) and EBV-negative adult Burkitt lymphoma (BL). DLBCL-NOS tumors underwent targeted capture sequencing using a panel of 125 genes recurrently mutated in aggressive B-cell lymphomas. BL biopsies were drawn from the Burkitt Lymphoma Genome Sequencing Project and had available WGS (dbGaP Study Accession: phs000527.v18.p6).

  Study EGAS50000000932

• Germline WES of serrated polyposis syndrome

  The serrated polyposis syndrome (SPS) is a disease with a mainly unknown inherited genetic basis characterized by the presence of multiple and/or large serrated polyps in the colon and a higher associated risk for colorectal cancer (CRC). The objective of the present study was to identify new SPS/CRC germline predisposition genes by using whole-exome sequencing in two affected SPS patients from the same family.

  Study EGAS50000000765

• ACUITI

  This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in patients with metastatic HR+/HER2- breast cancer receiving endocrine therapy and CDK4/6 inhibitors.

  Study EGAS50000000962

• Evaluation of the ERa binding region activity in breast and endometrial cancer

  Evaluate the activity of ERa binding site activity in breast and endometrial cancer.

  Study EGAS50000000009

• STARR-seq of ERa binding sites in MCF7 and Ishikawa cell lines

  A oligo-captured STARR-seq library was generated using as targets ERa binding regions indetified by ChIP-seq in Ishikawa (Endometrial cancer) and T47D (breast cancer) cell lines and, breast cancer primary tissues. STARR-seq assays have been performed in MCF-7 and Ishikawa cell lines. Cells have been cultured for 3 days in hormone deprivated (phenol-red free) media and stimulated for 6 hours by 10nM estradiol (E2) or DMSO (negative control).

  Dataset EGAD50000000015

• ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer - WGS

  Whole genome sequencing data related to the publication "ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer." ERBB2 alterations, usually amplifications or activating mutations, are seen in up to 20% of urothelial carcinoma and can be targeted by monoclonal antibodies, small molecule inhibitors, and most recently, antibody-drug conjugates. Here, we perform targeted and whole-genome sequencing of cell-free DNA and archival FFPE of mUC with and without ERBB2 alterations to identify unique genomic and clinical features of ERBB2-altered cancers, accompanied by IHC, FISH, and detailed clinical outcomes.

  Study EGAS50000001082

• ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer - Targeted

  Targeted sequencing data related to the publication titled "ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer." ERBB2 alterations, usually amplifications or activating mutations, are seen in up to 20% of urothelial carcinoma and can be targeted by monoclonal antibodies, small molecule inhibitors, and most recently, antibody-drug conjugates. Here, we perform targeted and whole-genome sequencing of cell-free DNA and archival FFPE of mUC with and without ERBB2 alterations to identify unique genomic and clinical features of ERBB2-altered cancers, accompanied by IHC, FISH, and detailed clinical outcomes.

  Study EGAS50000001081

• Enhancer profiling to identify identifies epigenetic markers of endocrine resistance in metastatic castration resistant prostate cancer patients

  Study EGAS00001006161

• Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer

  Emergence of resistance to immune checkpoint blockade (ICB) mandates the development of strategies for ICB sensitization. We aimed to understand the effects of epigenetic priming in re-shaping the tumor microenvironment, together with molecular drivers of therapeutic response of epigenetic therapy followed by ICB in non-small cell lung cancer (NSCLC; NCT01928576). This was done through a multi-omic approach encompassing both genomic and transcriptomic analyses. Findings suggest that epigenetic therapy may reshape the tumor microenvironment towards a more inflamed phenotype and prime responses to immunotherapy.

  Study EGAS50000000913

• Study of biomarkers implicated in radio-immunotherapy response in metastatic cancer

  Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the analysis from the SABR-PDL1 (NCT02992912) trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in patients with advanced cancer.

  Study EGAS50000001149

• Multi-omic dataset utilized in the analysis of a phase II study of epigenetic priming followed by nivolumab in lung cancer

  This dataset includes sequence files from whole exome sequencing and bulk RNA sequencing of tissue and blood biospecimens from a phase II clinical trial investigating epigenetic priming followed by immune checkpoint blockade in non-small cell lung cancer (NSCLC; NCT01928576). There are 78 whole exome sequencing files and 36 bulk RNA sequencing files included in this dataset.

  Dataset EGAD50000001336

• Study of biomarkers implicated in radio-immunotherapy response in metastatic cancer

  RNA sequencing data of tumors from 53 patients with advanced or metastatic cancer

  Dataset EGAD50000001644

• DAC for EGA study: Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer

  This is the Data Access Committee for the EGA study: Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer (temp ID 800).

  Dac EGAC50000000563

• Identifying genetic variants that alter TCR usage in the peripheral repertoire

  The relationship between genetic variation and CD8+ T-cell receptor (TCR) repertoire usage in patients receiving Immune Checkpoint Blockade (ICB) therapy for cancer is unexplored. We have conducted a genome-wide and human leukocyte antigen (HLA)-focused analysis of CD8+ T-cell TCR repertoire to identify genetic determinants of variable gene (V-gene) and CDR3 K-mer usage from samples taken prior to and after ICB (n=250). We identify 11 cis and 10 trans V-gene associations, primarily to the MHC, that meet genome-wide significance. TCR clones containing HLA associated V-genes were less stable across treatment, whilst at the single-cell level, genetically associated clones demonstrate subset enrichment and increased tumor reactivity expression profiles. Notably, patients with HLA-matched TCR clones demonstrate improved overall survival. Our work indicates a complex relationship between genotype and TCR repertoire in the context of ICB treatment, with novel implications for understanding factors relating to therapeutic response and patient outcomes.

  Study EGAS00001008189

• The dataset for Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types

  The dataset for “Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types” includes 288 bam files from whole genome, whole exome and targeted next-generation sequencing on the Illumina HiSeq2500 and MiSeq. The samples analyzed include tumor and normal tissue samples from patients with cancer.

  Dataset EGAD50000000744

• Southern African Prostate Cancer Study (SAPCS) 70 whole bloods

  new 70 germline WGS data of prostate cancer patients

  Dataset EGAD50000001626

• DAC for Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types

  While endometrioid and mucinous ovarian cancers represent nearly a quarter of ovarian cancers, their molecular characteristics and pathologic origins are poorly understood. To characterize the genomic and epigenomic alterations of these ovarian cancer subtypes and evaluate links to morphologically similar tumors from other sites, we performed sequence, copy number, mutation signature, rearrangement, and methylation analyses from tumor samples and matched normal tissues of 133 patients. These analyses included patients with ovarian endometrioid (n=44), ovarian mucinous (n=43), uterine endometrial (n=15), and gastrointestinal mucinous cancers (n=31). In addition to identifying genes previously known to be involved in these tumors, we identified alterations in RAD51C, NOTCH4, SMARCA1/4 and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous cancers. Whole genome sequencing revealed rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid tumors, and NF1 and MED1 in ovarian mucinous cancers. The number of alterations and affected genes in ovarian and uterine endometrioid cancers were similar as were genome-wide methylation profiles, suggesting that these tumors may have a similar tissue of origin. By contrast, methylation patterns in ovarian mucinous cancers were more similar to other gastrointestinal mucinous cancers, including mucinous cancers of the stomach, colon, and pancreas. These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.

  Dac EGAC50000000341

• LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients

  Study EGAS00001007072

• Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer (NABUCCO Cohorts 1 and 2)

  Study EGAS00001004521

• Ultra-Low-Pass Whole Genome Sequencing of Cell-Free DNA for Large B-Cell Lymphoma

  While deep targeted DNA sequencing of liquid biopsies has shown prognostic utility in large B-cell lymphoma (LBCL), the routine clinical adoption of these assays remains limited due to their high costs. Here, leveraging a well-annotated cohort of encompassing both frontline and relapsed/refractory (R/R) LBCL, we profiled patient plasma samples with two complementary modalities – ultra-low-pass whole genome sequencing (ulpWGS) and deep targeted DNA sequencing, the former being a cost-effective method to profile large scale chromosomal abnormalities and estimate tumor burden. Our findings revealed a strong association of high cell-free tumor burden by both genomic profiling modalities with established measures of tumor burden and patient survival. Notably, the associations with survival remained statistically significant after accounting for international prognostic index scoring. Furthermore, we showed that del(17p) in circulating tumor DNA as detected by ulpWGS was strongly associated with TP53 mutation status and predicted for significantly inferior patient outcome in frontline but not R/R LBCL patients. Our study demonstrates that ulpWGS can provide robust prognostic biomarkers for both frontline and R/R LBCL, highlighting its broad applicability for risk stratification.

  Study EGAS50000001027

• Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in endometriod carcinomas

  The mammalian SWI/SNF (mSWI/SNF) family of chromatin remodelers govern cell type-specific chromatin accessibility and gene expression and assemble as three distinct complexes: canonical BAF (cBAF), Polybromo-associated BAF (PBAF), and non-canonical BAF (ncBAF). ARID1A and ARID1B are paralog subunits that specifically nucleate the assembly of cBAF complexes and are frequently dual deleted in highly aggressive differentiated endometrial carcinomas (DECs). Here, in cellular models and primary human tumors, we find that ARID1A/B-mediated cBAF loss results in increased ncBAF and PBAF biochemical abundance and function genome-wide to maintain the DEC oncogenic signature. Further, treatment of ARID1A/1B-mutant cell lines and PDX models in vivo with a clinical-grade SMARCA4/2 ATPase inhibitor, FHD-286, markedly attenuates cell proliferation and tumor growth, and synergizes with carboplatin-based chemotherapy. Taken together, these findings reveal the oncogenic contributions of shifted of mSWI/SNF family complex abundance and chromatin-level gene regulatory functions and suggest therapeutic utility of mSWI/SNF complex small molecule inhibitors in dedifferentiated endometrial carcinoma and other cBAF-disrupted cancer types.

  Study EGAS50000001004

• Diversity of U1 small nuclear RNAs and Evaluation of Diagnostic Methods for their Mutations

  U1 small nuclear RNA (snRNA) mutations are recurrent non-coding alterations found in various malignancies, including medulloblastoma, yet their identification has proven challenging due to their repetitive nature. To establish a robust DNA-based, and RNA-based method for detecting U1 snRNA mutations, we performed targeted DNA sequencing using our original gene panel for medulloblastoma and RNA-sequencing. As an RNA-based method, we developed a random forest classifier employing splicing patterns which were massively altered as a result of U1 snRNA mutations. By using both methods, we successfully detected U1 snRNA mutation in five DNA samples and four RNA samples.

  Study EGAS50000000693

• SCANDARE HNSCC

  Prospective biobanking study in SCANDARE HNSCC (Head and Neck Squamous Cell Carcinoma) patients aiming at better understand the link between the molecular alterations of the tumor itself, its microenvironment and immune response.

  Study EGAS50000001158

• SCANDARE ovarian

  Prospective biobanking study in ovarian cancer patients aiming at better understand the link between the molecular alterations of the tumor itself, its microenvironment and immune response.

  Study EGAS50000001161

• SCANDARE ovarian WES data

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 91 frozen samples (n = 53 at baseline, n = 31 Post-NAC, n= 7 Recurrence, and n = 62 germline DNA) from 64 ovarian cancer patients using WES technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001658

• Predicting resistance to chemotherapy using chromosomal instability signatures

  The aim of this study is to assess whether three chromosomal instability signature biomarkers are capable of predicting resistance to standard chemotherapies, namely platins, taxanes and anthracyclines. As part of this study we compiled a proof of principle cohort of ovarian cancers treated with these therapies, profiled using the Illumina TSO500 panel. Analysis of these data demonstrated that accurate biomarker calling can be computed from these gene panel data.

  Study EGAS50000000992

• Final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial evaluating peri-operative atezolizumab for early-stage triple-negative breast cancer

  In IMpassion031, adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate (primary endpoint) for stage II/III triple-negative breast cancer (TNBC). Patients with stage II/III TNBC were randomized 1:1 to neoadjuvant chemotherapy plus peri-operative atezolizumab or pre-operative placebo. Descriptive secondary endpoints included event-free, disease-free, and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival HR 0.76, 95% CI: 0.47–1.21). Among patients without pCR, 14/70 (20%) atezolizumab-treated and 33/99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory analyses, pCR was prognostic for long-term outcome. Patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. Adding atezolizumab to chemotherapy for stage II/III TNBC is associated with more favorable long-term outcomes. ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935

  Study EGAS50000000974

• Sequenced IDH wildtype, untreated, human glioblastoma samples (GB-UK cohort)

  BAM files for 42 IDH wildtype, untreated, human glioblastoma samples from the GB-UK cohort, published in Noorani & Haughey et al. Cancer Discovery (2025).

  Dataset EGAD50000001649

• DynaTag for efficient profiling of transcription factors in small samples and single cells

  Systematic discovery of transcription factor (TF) landscapes in low-input samples and at single cell level is a major challenge in the fields of molecular biology, genetics, and epigenetics. To address this, we present here cleavage under Dynamic targets and Tagmentation (DynaTag), which allows robust mapping of specific TF-DNA interactions via the use of a physiological salt solution during sample preparation. Using this method, we revealed occupancy alterations for 15 different TFs in stem cell and cancer tissue models. Of note, we showcased for NANOG, MYC, and OCT4 differentially occupied genomic loci during stem cell differentiation, both in bulk and at single-cell resolution. DynaTag demonstrated superior signal-to-background ratio and occupancy resolution in comparison to CUT&RUN and ChIP-seq. In addition, a model for small cell lung cancer chemotherapy treatment in vivo showed increased chromatin occupancies of the gain-of-function mutant P53 p.R248Q, FOXA1, and MYC at altered gene pathways, such as epithelial-mesenchymal-transition. Altogether, these results highlight the technical advancement of DynaTag to uncover TF landscapes in cell models and in tissues of a complex disease model.

  Study EGAS50000001074

• Aberrant EZHIP Expression Drives Tumorigenesis in Osteosarcoma

  Study EGAS00001007531

• A Prospective Study of the Oral Microbiome and Pancreatic Cancer

  Two prospective cohort studies - the Black Women's Health Study and the Southern Community Cohort Study - were used to investigate the oral microbiome in relation to pancreatic cancer risk. Using a nested case-control study design, 148 cases and 510 matched controls were included (122 Black American pancreatic cancer cases and 409 matched controls). DNA was extracted from oral wash samples, using the PowerSoil Pro kit. Paired-end whole metagenomic shotgun sequencing was performed, using the Illumina HiSeq2000 platform with a read length of 100 bp (insert size 350 bp).

  Study phs002454

• Profiling Genome-Wide Circulating ncRNAs for the Early Detection of Lung Cancer

  Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Although imaging techniques such as low-dose computed tomography (LDCT), combined with tissue biopsies, have improved early detection rates, current diagnostic approaches are often limited by high false-positive rates, invasiveness, and radiation exposure, which lead to misdiagnosis and increased patient burden. Therefore, there is an urgent need for minimally invasive, accurate, and safe diagnostic biomarkers, particularly those derived from liquid biopsies such as blood-based exosomal RNA.This dataset specifically focuses on plasma-derived exosomal small non-coding RNAs (sncRNAs).A total of 233 de-identified plasma samples were obtained from Rush University Medical Center, including 116 NSCLC patients and 117 non-cancer controls. Exosomes were isolated from plasma, RNA was extracted, and small RNA sequencing was performed using the Illumina NextSeq 500 platform. Data available through dbGaP include individual-level raw sequencing files (FASTQ) and basic phenotype annotations of the plasma cohort.A diagnostic model was initially developed using small RNA-seq data from 1,446 tissue samples obtained from TCGA and GEO, identifying a robust sncRNA signature that distinguished NSCLC from non-cancer samples with an AUC of 0.90 in hold-out tissue validation. This signature was subsequently validated in the plasma exosome cohort, achieving an AUC of 0.84 in independent validation. The model demonstrated consistent diagnostic performance across subgroups stratified by age, sex, smoking history, cancer stage, and NSCLC subtype. Survival and functional analyses further supported the clinical and biological relevance of the identified sncRNAs. It is hoped that this resource will contribute to a better understanding of the sncRNA expression landscape in NSCLC and promote the development of non-invasive biomarkers for early cancer detection. These data may be applied to the investigation of transcriptomic and other risk factors, provide insight into cancer screening, tumor progression mechanisms, and prognosis prediction, and ultimately support precision medicine for NSCLC.

  Study phs004166

• A Translational, Pharmacodynamic and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer

  This phase IB clinical trial studied the pharmacodynamic changes induced by everolimus in patients with previously untreated, resectable non small cell lung cancer. Using a combination of in vivo and ex vivo assessments with FDG PET, immunohistochemistry and genomic assays, evidence of mTOR pathway perturbation was assessed in patients treated with everolimus, an allosteric mTOR inhibitor. Untreated patients served as controls for comparison. Key results from this work include a dose-dependent biologic effect of everolimus, signal of activity in RAS mutant tumors as well as near complete metabolic and pathologic response in a case of sarcomatoid lung cancer. These findings represent novel translational insights that can guide future development of mTOR inhibitors in lung cancer and other tumor types. Additionally, metabolic response and anatomic tumor shrinkage observed in a significant proportion of patients following a short of duration of therapy with everolimus suggests potential clinical utility of this agent in carefully-selected lung cancer patients.

  Study phs000829

• National Cancer Institute (NCI) Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Colon, Kidney, Liver, Multiple Myeloma, and Prostate among Racially and Ethnically Diverse Populations

  The Early Onset Malignancies Initiative (EOMI) is focused on collecting specimens from racially and ethnically diverse population groups with six different types of cancer (breast, prostate, colon, liver, kidney, and multiple myeloma). This initiative is a partnership between the Center for Research Strategy, the Center for Cancer Genomics and the Division of Cancer (DCP). DCP's NCI Community Oncology Research Program (NCORP) is a critical partner. The acquisition of the cancer and matching normal biospecimens in this initiative are from newly diagnosed early onset cancer patients who identify as Non-Hispanic Black, Hispanic, American Indian or Alaska Native, or Non-Hispanic White. The Minority/Underserved NCORPs sites will collect the samples for this project. By carrying out this initiative in the NCORP's national network of investigators, cancer care providers, and research institutions, the EOMI will harness the community-based partnerships to improve participation among these racial/ethnic groups. The NCORP investigators, as participants in NCI's clinical trials network, will annotate the biologic samples with clinical information that will enhance the ability to answer questions about molecular determinants of early disease, treatment response, and/or prognosis. The EOMI will be a step forward in addressing racial/ethnic disparities and in understanding cancer in underserved populations.

  Study phs001952

• single cell data from HPV-positive head and neck cancer patients receiving induction CTLA-4 and PD-1 immune checkpoint blockade

  Baseline and on-treatment tumor samples from human papillomavirus-positive oropharynx cancer patients receiving anti-CTLA-4 and anti-PD-1 immune checkpoint blockade were analyzed by single-cell RNA and TCR sequencing.

  Study EGAS50000000335

• Enhancer profiling identifies epigenetic markers of endocrine resistance and reveals therapeutic options for metastatic castration-resistant prostate cancer patients (LuCaP cell line data)

  Androgen Receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops. Using metastatic samples from a prospective phase II clinical trial, we epigenetically profiled enhancer/promoter activities with H3K27ac chromatin immunoprecipitation followed by sequencing, before and after AR-targeted therapy. We identified a distinct subset of H3K27ac-differentially marked regions that associated with treatment responsiveness. These data were successfully validated in mCRPC patient-derived xenograft models (PDX). In silico analyses revealed HDAC3 as a critical factor that can drive resistance to hormonal interventions, which we validated in vitro. Critically, we identified the pan-HDAC inhibitor, vorinostat to be effective in decreasing tumor cell proliferation both in vitro and in vivo. Moreover, we uncovered evidence for HDAC3 working together with Glucocorticoid Receptor (GR) as a potential mechanism for this therapeutic effect. These findings demonstrate rationale for new therapeutic strategies including HDAC inhibitors to improve patient outcome in advanced stages of mCRPC. Project Goal: We identified H3K27ac regions associated with resistance in patient samples. Extensive analysis of these regions suggested that HDAC3 may play a role in resistance. To test this, we analyzed ChIP-seq and RNA-seq from cell lines generated from PDX LuCaP samples (recapitulating resistant and non-resistant) to validate findings in patient samples. ChIP-seq samples were used to verify the signals identified from specific factors, such as H3K27ac, AR, FOXA1, GR and HDAC3, their association with resistance and possible mechanisms of action. RNA-seq samples were analyzed to determine the effect of AR signaling in these samples in specific genes in the H3K27ac resistance-associated regions.

  Study EGAS50000000917

• HSC_population_dynamics_KSP_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001002762

• MutWP6__CRUK_Grand_Challenge_Mutographs_of_Cancer__Botseq

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Within Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans. Whole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.

  Study EGAS00001004330

• COMPASS Next Generation Sequencing WGS data

  Whole genome sequencing data for Pancreatic Cancer Samples from the COMPASS clinical trial

  Study EGAS50000001091

• UCL Translation Uro-Oncology Data Access Committee will govern access to data generated from the Translation Uro-Oncology groups of the UCL Cancer Institute and UCL Division of Surgery & Interventional Science

  Dac EGAC00001000471

• Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study

  Lung cancer, especially non-small cell lung cancer (NSCLC), has high mortality rates. Early-stage NSCLC shows a 50% relapse rate post-surgery, with most recurrences occurring within two years and a 5-year survival of only 30%. This study focuses on the prognostic value of circulating miRNAs in surgically treated ES-NSCLC patients, aiming to assess their predictive accuracy and compare them to standard prognostic factors.

  Study EGAS50000001032

• Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration

  The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. We used continuous long-read sequencing of oropharyngeal cancers and cervical cancer cell lines to resolve structural variation induced by HPV. We discovered a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer.

  Study phs003396

• The Haplotype-Resolved Genome and Epigenome of the Aneuploid HeLa Cancer Cell Line

  The genomic architecture of HeLa remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq and ENCODE Project data sets to phase the HeLa epigenome. This revealed strong, haplotype specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes. Reprinted from Adey et. al. 2013, Nature, with permission from Nature Publishing Group.

  Study phs000642

• DNA Repair Capacity for Lung Disease Risk Assessment

  A focus of this work was to address the extent to which susceptibility for lung cancer varies by gene-environment-phenotype interactions involving DNA repair capacity and differences in risk from environmental stressors. GWAS from a subset of subjects from the Lovelace Smokers Cohort and New Mexico Lung Cancer cohort were used to derive polygenic risk scores for DNA repair pathways (nucleotide excision, base excision, single strand break, non-homologous, homologous recombination). Logistic regression analysis was used to examine the association between polygenic risk score and lung cancer status. Polygenic risk scores were grouped by quartiles. Only diminished base excision repair was associated with increased risk for lung cancer at the 25-50% quartile and approached significance at the 50-75% quartile.

  Study phs004063

• APOBEC Mutagenesis, Kataegis, Chromothripsis in EGFR-Mutant Osimertinib-Resistant Lung Adenocarcinomas

  Expanding on studies investigating apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) mutagenesis in histological transformation of epidermal growth factor receptor (EGFR)-mutant lung cancers, it has been hypothesized that mutational signature analysis may help better understand acquired resistance to targeted therapies. Using mutational signature analysis in Receptor Tyrosine Kinase (RTK) driven lung adenocarcinomas, more specifically EGFR mutant lung cancer, APOBEC dominant mutational signatures were noted more frequently in subclonal post Tyrosine Kinase Inhibitor (TKI) treatment biospecimen samples and in the presence of large-scale genomic rearrangements. This is hypothesized to be due to the pressure of treatment with TKIs; a fact that should be further explored and can be potentially manipulated in order to overcome drug resistance.

  Study phs003812

• HeLa Cell Genome Sequencing Studies

  HeLa is a human epithelial adenocarcinoma cell line that was derived from biopsy specimens of a 31-year old patient named Henrietta Lacks who was being treated for cervical cancer at The Johns Hopkins University Hospital in 1951. The specimens were obtained without her knowledge or consent just before her death in 1951. HeLa is the oldest and most widely used human cell line and has been an extraordinarily important resource for researchers throughout the world. HeLa cells have served as a standard for understanding many fundamental biological processes, such as testing the polio vaccine, establishing basic techniques for cloning and in vitro fertilization, identifying the cause of cervical cancer (HPV), and advancing the development of anti-cancer drugs.This study contains all authorized whole genome sequence data of the HeLa cell line from datasets currently in dbGaP. These data have been approved for health, medical, and/or biomedical research purposes. Access to these data can be granted for one year. Accessible data will include the studies listed on this page and any additional authorized datasets that become available during this one-year period. The HeLa Genome Data Access Working Group of the Advisory Committee to the Director (ACD) will review requests from the research community for access to these datasets and assess whether the requests align with the terms of use defined in the HeLa Genome Data Use Agreement. The Working Group's findings will be reported to the ACD, and the ACD will make recommendations to the NIH Director about whether a request should be approved or disapproved. The NIH Director will decide whether access to the data will be granted.

  Study phs000640

• Tumor-associated neutrophil 1 precursors impair homologous DNA repair and promote sensitivity to PARP-inhibition

  Tumor evolution is one of the major mechanisms responsible for acquiring therapy resistant and more aggressive cancer clones. Whether the tumor microenvironment through immune-mediated mechanisms might promote the development of more aggressive cancer types is crucial for the identification of additional therapeutical opportunities. Here, we identify a subset of tumor-associated neutrophils, defined as tumor-associated neutrophil precursors (PreNeu). These PreNeu are enriched in highly proliferative hormone-dependent breast cancers and impair DNA repair capacity

  Study EGAS00001008154

• WES data of pediatric cancer patients with P/LP variants in HBOC-related genes

  The current study aimed to identify (likely) pathogenic germline variants(LP/PVs) in 25 adult-onset HBOC-related genes within a cohort of 372 pediatric cancer patients. For this purpose we performed (paired-end) whole exome sequencing (WES) using Ilumina sequencing technology. The files uploaded here belong to the 27 individuals with such a LP/PV. The project provides insight into the prevalence and spectrum of such variants in childhood cancer, contributing to the understanding of genetic predisposition in pediatric oncology.

  Dataset EGAD50000001561

• Clonal hematopoiesis in metastatic urothelial and renal cell carcinoma

  This study aimed to determine the prevalence and clinical relevance of clonal hematopoiesis in metastatic urothelial and renal cell carcinoma.

  Study EGAS50000000870

• University of Sydney Thyroid Cancer Data Access Committee

  This Data Access Committee (DAC) manages access to genomic data generated by the Thyroid Cancer Research Group at the University of Sydney and Royal North Shore Hospital. The DAC will evaluate data access requests to ensure they align with participant consent and the conditions approved by the Northern Sydney Local Health District Human Research Ethics Committee. Requests will be reviewed for scientific validity, alignment with the original consent, and compliance with institutional and regulatory data governance policies.

  Dac EGAC50000000661

• Biomarker Research for Anti EGFR Monoclonal Antibodies by Comprehensive Cancer Genomics

  The purpose of this study is to explore new biomarkers for predicting the effectiveness of an anti-epidermal growth factor receptor (anti-EGFR) antibody in patients with advanced colorectal cancer. The investigation involves analyzing the entire exome, conducting a genome-wide association study (GWAS), and analyzing copy number variations (CNVs) using single nucleotide polymorphism (SNP) arrays. Genetic material from both cancerous and non-cancerous tissues, as well as blood samples from patients who received the antibody treatment, will be used. The goal is to identify genetic mutations and SNPs associated with treatment efficacy and adverse events, and to assess the correlation between their presence and treatment effectiveness using statistical methods.

  Study JGAS000779

• Identification of colorectal cancer susceptibility genes in Japanese

  We performed whole genome sequencing of 617 colorectal cancer patients registered in BioBank Japan to identify novel susceptibility genes.

  Study JGAS000699

• Developing therapeutics for ovarian cancer using ovarian cancer organoids

  To identify effective drugs for clear cell ovarian cancer (CCC) and high-grade serous ovarian cancer (HGSC) through high-throughput drug screening using ovarian cancer organoids and to identify novel therapeutic targets based on the biological characteristics of CCC and HGSC through omics analysis.

  Study JGAS000764

• Elucidating the development of cervical cancer and identifying therapeutic targets based on cancer genome analysis.

  The objective of this project is to analyze genomic aberrations and gene expression changes, such as mutations, deletions, and amplifications, in human cervical cancer cells at the somatic cell level, and to contrast these with clinicopathological information to elucidate the molecular mechanisms and characteristics of lcervical cancer development and progression at the genetic level.

  Study JGAS000803

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established three kinds of esophageal tumoroids derived from esophageal cancer patient. We performed whole exome sequencing to analyze genetic background of the tumoroids.

  Study JGAS000749

• Atezolizumab monotherapy following dCRT indicated a promising cCR rate in patients with unresectable locally advanced esophageal squamous cell carcinoma (EPOC1802)

  The objective is to analyze tumor and normal cell exome sequencing of esophageal cancer patients participating in the Tenergy trial before treatment and RNA sequencing specimens of tumor biopsy specimens at three points before treatment, after radiation chemotherapy, and after atezolizumab administration, in order to search for biomarkers to predict treatment response. Exome sequencing of pretreatment tumor tissue (27 specimens) and normal tissue (27 specimens) from esophageal cancer patients participating in the Tenergy trial, and RNA sequencing of tumor biopsy specimens at three time points before treatment (28 specimens), after radiation chemotherapy (25 specimens) and after atezolizumab administration (25 specimens).

  Study JGAS000708

• Evaluation of novel therapies using primary cultured gynecological cancer cells and search for predictors of efficacy

  The objective of this study is to establish an optimal method to evaluate the anti-tumor efficacy and biological activity of the novel therapies under investigation in our department using cancer tissues and cells derived from patients with gynecological malignancies in vitro and to evaluate them in practice. This research will contribute to the development of new treatments for gynecological cancer.

  Study JGAS000809

• Application of targeted long-read methylation sequencing to dissected breast cancer tissues

  Four regions defined by pathological view were dissected from fresh frozen sections of breast cancer tissue using Millisect system. DNA and RNA extracted from the dissected tissues were applied to short-read WGS, short-read RNA-seq, short-read EM-seq, and targeted long-read methylation analysis t-nanoEM.

  Study JGAS000758

• Identification of gastric cancer susceptibility genes in Japanese

  We performed whole genome sequencing of 256 gastric cancer patients registered in BioBank Japan to identify novel susceptibility genes.

  Study JGAS000698

• PD-1 antibody-bound progenitor-exhausted CD8+ T cells in lymph nodes boost PD-1-blockade anti-tumor immunity in gastrointestinal cancer

  While progenitor-exhausted T cells (Tpex) expressing TCF1 and PD-1 are crucial for the therapeutic effect of immune checkpoint inhibitors (ICIs; therapeutic anti-PD-1 antibodies), the dynamics of ICI-bound Tpex are not fully understood. In this study, we investigated ICI-bound T cells in detail using combined sequencing analysis at the single cell level. By analyzing samples from gastrointestinal cancer patients with or without ICI treatment, we found that Tpex were enriched in proximal lymph nodes (LNs) and proliferated at a high rate after ICI treatment. Importantly, ICI high-bound Tpex in LNs shared T-cell receptor clonotypes with intratumoral exhausted CD8+ T cells (Tex), suggesting their migration to tumor sites after ICI treatment. These findings indicate that ICIs initially target PD-1+CD8+ Tpex in LNs, prompting their proliferation. Subsequently, these cells migrate to tumors and differentiate into Tex, thereby exerting anti-tumor immunity.

  Study JGAS000720

• Elucidation of the association of the HPV integration and oropharyngeal cancer

  Whole-genome sequencing was performed using tumor and blood samples from 14 patients with HPV-associated oropharyngeal cancer. Bulk RNA sequencing was performed using tumor samples from 19 patients with HPV-associated oropharyngeal cancer and 17 patients with non-HPV-associated oropharyngeal cancer and normal tonsil samples from 2 healthy controls.

  Study JGAS000751

• Development of actionable molecular targets and/or biomarkers for prognostication and patient stratification in gynecological cancer based on whole-exome sequencing and epigenomic analysis

  We collected 92 endometrial hyperplasia lesions (48 non-atypical from 30 cases and 44 atypical from 24 cases) and matched normal tissues/whole blood. The purpose of this study is to develop actionable molecular targets and/or biomarkers for prognostication and patient stratification.

  Study JGAS000642

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established a kind of lung cancer tumoroids derived from a mucus-producing solid pulmonary adenocarcinoma patient. We performed whole exome sequencing and RNA sequencing to analyze genetic background of the tumoroids.

  Study JGAS000664

• Transcriptome sequencing of human colon organoid after co-cultivation with Bifidobacterium longum

  The large intestine has a dense milieu of indigenous bacteria, generating a complex ecosystem with crosstalk between individual bacteria and host cells. In vitro host cell modeling and bacterial interactions at the anaerobic interphase have elucidated the crosstalk molecular basis. Although classical cell lines derived from patients with colorectal cancer including Caco-2 cells are used, whether they adequately mimic normal colonic epithelial physiology is unclear. To address this, we performed transcriptome profiling of Caco-2 and Monolayer cells derived from healthy Human Colonic Organoid (MHCO) cultured hemi-anaerobically. Coculture with the anaerobic gut bacteria, Bifidobacterium longum subsp. longum differentiated the probiotic effects of test cells from those of physiologically normal intestinal and colorectal cancer cells. We cataloged non- or overlapping gene signatures where gene profiles of Caco-2 cells represented absorptive cells in the small intestinal epithelium, and MHCO cells showed complete colonic epithelium signature, including stem/progenitor, goblet, and enteroendocrine cells colonocytes. Characteristic gene expression changes related to lipid metabolism, inflammation, and cell-cell adhesion were observed in cocultured live Bifidobacterium longum and Caco-2 or MHCO cells. B. longum-stimulated MHCO cells exhibited barrier-enhancing characteristics, as demonstrated in clinical trials. Our data represent a valuable resource for understanding gut microbe and host cell communication.

  Study JGAS000740

• RNA sequencing of surgically removed lung adenocarcinoma afterwards treated with immune checkpoint inhibitors

  Patients with lung adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) database were enrolled in the training cohort to establish a prognostic signature based on the expression of tumor-specific amino acid metabolism related genes. The established signature was further investigated against an original cohort, KCC-ICI, of chemotherapy combined with immune checkpoint inhibitors. The signature consisting of nine genes, KYNU, PSPH, PPAT, MIF, GCLC, ACAD8, TYRP1, ALDH2, and HDC, could effectively stratify the OS in LUAD patients. The KCC-ICI cohort confirmed the predictive ability of the established signature in the clinical response to immune checkpoint blockade therapy, which correlated with the infiltration of immune cells (e.g., T lymphocytes and nature killer cells). We discovered that the high signature risk score patients showed a significantly lower concentration of plasma-free ??-aminobutyric acid (AABA).

  Study JGAS000675

• 1. Identidication of molecular biological mechanism associated with the development and prognosis of uterine cancer, uterine sarcoma, and endometrial hyperplasia / 2. Identification of molecular biological mechanism associated with the development of endometriosis and malignant transformation, ovarian cancer, fallopian tubal cancer, peritoneal cancer, and other malignant tumors in gynecological organs

  To clarify the biological difference between clear cell carcinoma and other histological subtypes in ovarian carcinomas by comparing copy number variants, and to identify molecular subtypes and carcinogenesis in clear cell ovarian carcinomas by whole-exome sequencing and RNA-sequencing. Then, characterize high-grade serous carcinomas by NGS-based, integrative genomic analyses, with focus on homologous recombination deficiency, molecular subtypes, prognostic factors and effectiveness of PARP inhibitor. Based on the results of whole-exome sequencing, an investigator-initiated, phase 2 clinical trial will be conducted to evaluate the efficacy and safety of the PARP inhibitor olaparib in HRD-positive cases.

  Study JGAS000789

• Spatial omics analysis of non-small cell lung cancers for revealing molecular statuses of intratumor heterogeneity and tumor microenvironment

  In this study, we perform spatial transcriptome analysis Visium/Xenium and other omics analysis using surgical specimens of Japanese non-small cell lung cancer cases to understand omics statuses of cancer cells and their surrounding stromal and immune cells in local tumor regions. We aim to stratify lung cancer patients with considering intratumor heterogeneity and complicated microenvironent of lung cancer tissues by using spatial omics data and histopathological information.

  Study JGAS000613

• Whole genome sequencing data using Adaptive sampling from 33 patients with hereditary cancer syndrome

  We performed whole genome sequencing using adaptive sampling with GridION on 33 patients with clinically suspected hereditary cancer syndromes to evaluate an efficient computational workflow.

  Study JGAS000654

• Prevalence of rare pathogenic variants in cancer-predisposing genes among Japanese advanced prostate cancer patients.

  The prevalence of rare pathogenic variants in cancer-predisposing genes including those associated with DNA repair remains unknown among Japanese patients with advanced prostate cancer. This study was designed to elucidate the prevalence of pathogenic variants in 27 known cancer-predisposing genes and to explore the prognostic significance of the variants identified.

  Study JGAS000509

• Whole exome sequence in EGFR-TKI resistant non-small cell lung cancer

  Whole exome analysis to clear molecular basis and mutation spectrum in EGFR-TKI resistant non-small cell lung cancer

  Study JGAS000102

• Identification of gastric cancer susceptibility genes in Japanese

  We performed whole genome sequencing of 2067 gastric cancer patients registered in BioBank Japan to identify novel susceptibility genes.

  Study JGAS000701

• Exploring Genomic Mutations in Gastric Cancer among Japanese Populations

  We conducted a comprehensive analysis of whole-genome and RNA sequences obtained from biopsy samples of 65 patients with advanced gastric cancer prior to chemotherapy treatment.

  Study JGAS000754

• Amplicon sequencing of long non-coding RNA associated with gastritis and gastric carcinogenesis

  This study aimed to identify dysregulations of long non-coding RNA (lncRNA) in gastric cancer, and to reveal molecular functions of lncRNAs associated with gastritis and gastric carcinogenesis. We also aimed to reveal the correlation between clinicopathological characteristics and lncRNA alterations. To this end, we will try to develop predictive markers of gastric cancer risk, which enables prevention and early detection of gastric cancer. We will also try to develop molecular markers which enable us to select treatment strategies for gastric cancer.

  Study JGAS000353

• Multi-omic profiling of patient-derived pancreatic tumor organoids

  We conducted multi-omic profiling of patient-derived pancreatic cancer organoids and genetically engineered normal pancreas organoids.

  Study JGAS000719

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established three kinds of lung cancer tumoroids derived from three different pulmonary large cell neuroendocrine carcinoma patients. We performed whole exome sequencing to analyze genetic background of these kinds of tumoroids.

  Study JGAS000641

• Pilot study towards the development of a Companion/Complimentary Diagnosis platform using liquid biopsy with cfDNA for immune checkpoint inhibitor therapy in advanced urothelial cancer

  Preliminary analysis was conducted to develop a cfDNA-based platform capable of predicting gene mutation profiles, TMB, gene expression profiles (molecular subtype diagnosis), and immunohistochemical findings (PD-L1 expression) using the primary lesion tissue of bladder cancer and upper urinary tract epithelial cancer, verifying the feasibility of such development.

  Study JGAS000714

• Application of targeted long-read methylation sequencing to dissected lung cancer tissues

  To investigate DNA methylation patterns within the tumor microenvironment, multiple regions were dissected from fresh-frozen sections of two lung adenocarcinoma specimens using the Millisect system. These regions were annotated based on spatial transcriptome data. DNA samples extracted from these regions were subjected to targeted long-read methylation sequencing using t-nanoEM. To establish a control dataset, short-read whole-genome sequencing (WGS) was performed on the tumor and normal parts, and long-read WGS was performed on the tumor part.

  Study JGAS000757

• Evaluation of clonal hematopoiesis regarding TP53 mutation status in 140,597 individuals

  The existence of clonal hematopoiesis, in which somatic mutations accumulate in the peripheral blood with age and expand clonally, is becoming clear, and various clinical implications are being suggested. This study analyzed clonal hematopoiesis regarding TP53 mutation status by targeted sequencing in 140,597 individuals, including those with breast cancer, gastric cancer, colorectal cancer, heart failure, stroke, etc. The clinical characteristics of clonal hematopoietic carriers were evaluated.

  Study JGAS000782

• Amplicon sequencing of various tumors

  In our previous studies on advanced esophageal, gastric, and colorectal carcinomas, measurement of circulating tumor DNA (ctDNA) in terms of variant allele frequency (VAF) in blood suggested: (1) patients with high VAF have a high chance of relapse; (2) VAF changes in response to treatment; and (3) ctDNA VAF elevation precedes imaging diagnosis of relapse. It is thus necessary to investigate whether these findings can be generalized in a wide cancer spectrum, types of treatment, and relapse phenotypes across cancer types. In the present study, we conduct a non-interventional observational study in a wide cancer spectrum on the basis of technical establishment for ctDNA using our unique digital PCR probe library.

  Study JGAS000366

• 1. Identidication of molecular biological mechanism associated with the development and prognosis of uterine cancer, uterine sarcoma, and endometrial hyperplasia / 2. Identification of molecular biological mechanism associated with the development of endometriosis and malignant transformation, ovarian cancer, fallopian tubal cancer, peritoneal cancer, and other malignant tumors in gynecological organs

  To identify molecular subtypes and carcinogenesis in clear cell ovarian carcinomas by whole-exome sequencing, RNA-sequencing, and methylation array, and to characterize high-grade serous carcinomas by NGS-based, integrative genomic analyses, with focus on homologous recombination deficiency, molecular subtypes and prognositic factors.

  Study JGAS000560

• Spatiotemporal single-cell analysis reveals a time-dependent immunological modulation by multi-fractionated radiotherapy in esophageal cancer

  Description Here, by integrative spatial and single-cell analyses using spatial transcriptome (VISIUM) and single-cell RNA sequencing (scRNA-seq), we examined the spatiotemporal dynamics of immune-response in the tumor microenvironment of esophageal squamous cell carcinoma (ESCC) before, during and after RT. The comprehensive single-cell analyses demonstrated the infiltration of immune cells into tumor with the dynamic change of immune-stimulatory and -suppressive gene expression after RT. ScRNA-seq analysis uncovered the time- and cell-type-dependent alteration of gene expression profile from during to after RT. This datasets in the present study will provide the information of RT-induced gene signature to seek an appropriate target of personalized immunotherapy combined with radiotherapy and of determining the timing of the combination therapy.

  Study JGAS000712

• scMultiome analysis of human tongue cancer organoids

  We performed single-cell Multiome analysis (10X Genomics) of a uniquely established human tongue cancer organoids, including both chemo-sensitive organoids and chemotherapy resistant organoids.

  Study JGAS000606

• Trial of Onco-Panel for Geneprofiling to Estimate both Adverse events and Response by cancer treatment (TOP-GEAR)

  Bam files and fastq files in a hospital-based prospective study (TOP-GEAR project, the 2nd stage) to investigate the feasibility and utility of NGS-based analysis of 114 cancer-associated genes (the NCC Oncopanel test). DOI: 10.1111/cas.13969

  Study JGAS000662

• Single nucleus RNA sequencing of squamous cell carcinoma arising from mature teratoma of the ovary

  Squamous cell carcinoma arising from mature teratoma is one of the rare ovarian cancers. Therefore, the detailed molecular background of this disease has not been elucidated. The purpose of this study is to investigate the single-cell transcriptional landscape of this disease.

  Study JGAS000521

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established a kind of lung cancer tumoroids derived from a mucus-producing solid pulmonary adenocarcinoma patient. We performed whole exome sequencing and RNA sequencing to analyze genetic background of the tumoroids.

  Study JGAS000653

• Evaluation of whole genome sequencing utility in identifying driver alterations in cancer genome

  This study aimed to assess the effectiveness of whole genome sequencing (WGS) compared to whole exome sequencing (WES) in identifying driver alterations in cancer genomes. Out of 177 cases with no driver alterations detected by WES, WGS identified driver alterations in 68.4% and likely driver alterations in 22.6% of cases. The most common alterations found were oncogene amplifications, tumor suppressor gene deletions, and small variants outside coding regions. WGS proved valuable in uncovering genomic changes associated with cancer development.

  Study JGAS000715