15041 results for "cancer studies using rna-seq"

in 45.61 milliseconds.

• Illumina_WXS_MET-CELL-XEN

  Whole-exome sequencing on Illumina HiSeq2000/2500 of Patient-derived xenograft derived from PDO culture derived from colorectal cancer metastasis sample

  Dataset EGAD00001002097

• GEL WGS Comparison

  These samples are to be analysed with the CGP Developed cancer panel and the results will be compared with WGS data from 4 different comercial providers.

  Dataset EGAD00001000872

• Sequencing data for Murtaza et al. Nature Communications 2015 (doi:10.1038/ncomms9760)

  Exome and targeted amplicon sequencing data for tumor, germline and plasma samples from a patient with metastatic breast cancer.

  Dataset EGAD00001002108

• Illumina_WGS_T-XEN-CELL

  Whole-genome sequencing on Illumina HiSeq2000/2500 of PDO culture derived from Patient-derived xenograft derived from colorectal cancer primary tumor sample

  Dataset EGAD00001002092

• Genome and transcriptome sequence data from a NUT midline carcinoma tumor patient

  Genome and transcriptome sequence data from a NUT midline carcinoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015289

• Genome and transcriptome sequence data from a minimally invasive adenocarcinoma tumor patient

  Genome and transcriptome sequence data from a minimally invasive adenocarcinoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015297

• Illumina_RNA_T-CELL-XEN

  RNAseq on Illumina HiSeq2000/2500 of Patient-derived xenograft derived from PDO culture derived from colorectal cancer primary tumor sample

  Dataset EGAD00001002079

• Sequencing data for the manuscript "Multi-focal sampling of de novo metastatic prostate cancer reveals complex polyclonality and enables accurate clinical genotyping"

  This submission includes targeted and whole exome paired-end fastq files.

  Dataset EGAD00001009651

• 10x Single Cell Gene Expression Library SCRNA10X_SA_CHIP0175_001

  10x Single Cell Gene Expression library SCRNA10X_SA_CHIP0175_001 for Triple negative breast cancer patient-derived xenograft SA535X6XB03101

  Dataset EGAD00001011224

• Genome and transcriptome sequence data from a neurofibromatosis type 1 tumor patient

  Genome and transcriptome sequence data from a neurofibromatosis type 1 patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015301

• Genome and transcriptome sequence data from a metastatic alveolar rhabdomyosarcoma tumor patient

  Genome and transcriptome sequence data from a metastatic alveolar rhabdomyosarcoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015295

• Illumina_WGS_MET-CELL-XEN

  Whole-genome sequencing on Illumina HiSeq2000/2500 of Patient-derived xenograft derived from PDO culture derived from colorectal cancer metastasis sample

  Dataset EGAD00001002086

• 10x Single Cell Gene Expression Library SCRNA10X_SA_CHIP0150_002

  10x Single Cell Gene Expression library SCRNA10X_SA_CHIP0150_002 for Triple negative breast cancer sample SA609X5XB03231

  Dataset EGAD00001011213

• Genome and transcriptome sequence data from a acute lymphoblastic leukemia tumor patient

  Genome and transcriptome sequence data from a acute lymphoblastic leukemia patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015285

• scRNA mCRC PDO

  Chromium 10x scRNA of 6 metastatic colorectal cancer organoids

  Dataset EGAD00001008734

• Gastric Cancer Organoid Cultures and Tumors Whole Exome Sequencing Data

  Whole exome sequencing data generated from organoid cultures established from gastric cancers, paired gastric tumor frozen tissues and blood leukocyte DNA.

  Dataset EGAD00001004301

• Illumina_RNA_MET-CELL_Passages

  RNAseq on Illumina HiSeq2000/2500 of PDO culture derived from colorectal cancer metastasis sample at early/late passages

  Dataset EGAD00001002884

• Genome and transcriptome sequence data from a papillary thyroid carcinoma tumor patient

  Genome and transcriptome sequence data from a papillary thyroid carcinoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015303

• Genome and transcriptome sequence data from a relapsed wilms tumor tumor patient

  Genome and transcriptome sequence data from a relapsed Wilms tumor patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015304

• Illumina_RNA_T-XEN-CELL

  RNAseq on Illumina HiSeq2000/2500 of PDO culture derived from Patient-derived xenograft derived from colorectal cancer primary tumor sample

  Dataset EGAD00001002081

• Illumina_WGS_T-CELL-XEN

  Whole-genome sequencing on Illumina HiSeq2000/2500 of Patient-derived xenograft derived from PDO culture derived from colorectal cancer primary tumor sample

  Dataset EGAD00001002090

• 10x Single Cell Gene Expression Library SCRNA10X_SA_CHIP0079_001

  10x Single Cell Gene Expression library SCRNA10X_SA_CHIP0079_001 for Triple negative breast cancer sample SA1035X6XB03216

  Dataset EGAD00001011241

• Nanopore low-pass WGS of human brain tumors

  Nanopore low-pass WGS of human brain tumors for evaluation of DNA methylation-based classification of cancer

  Dataset EGAD00001009663

• Genome and transcriptome sequence data from a malignant rhabdoid tumour tumor patient

  Genome and transcriptome sequence data from a malignant rhabdoid tumour patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015310

• Genome and transcriptome sequence data from a recurrence nasopharyngeal rhabdomyosarcoma tumor patient

  Genome and transcriptome sequence data from a recurrence nasopharyngeal rhabdomyosarcoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015314

• Genome and transcriptome sequence data from a pineal parenchymal tumor tumor patient

  Genome and transcriptome sequence data from a pineal parenchymal tumor patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015317

• Spatial Maps of Prostate Cancer Transcriptomes

  A total of 14 samples that has been analyzed with the Spatial Transcriptomics method. H&E stain can be sent if requested.

  Dataset EGAD00001004121

• Genome and transcriptome sequence data from a choroid plexus carcinoma tumor patient

  Genome and transcriptome sequence data from a choroid plexus carcinoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015321

• Genome and transcriptome sequence data from a malignant rhabdoid tumor tumor patient

  Genome and transcriptome sequence data from a malignant rhabdoid tumor patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015323

• Genome and transcriptome sequence data from a NUT midline carcinoma tumor patient

  Genome and transcriptome sequence data from a NUT midline carcinoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015325

• Genome and transcriptome sequence data from a acute myeloid leukemia tumor patient

  Genome and transcriptome sequence data from a acute myeloid leukemia patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015331

• Colorectal organoids and tumour tissue

  Whole genome sequencing of single cell derived organoids from normal colon tissue and colorectal cancer.

  Dataset EGAD00001001447

• Illumina_WGS_MET-XEN

  Whole-genome sequencing on Illumina HiSeq2000/2500 of Patient-derived xenograft derived from colorectal cancer metastasis sample

  Dataset EGAD00001002087

• Genome and transcriptome sequence data from a fibrovascular brain tumor tumor patient

  Genome and transcriptome sequence data from a fibrovascular brain tumor patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015271

• Genome and transcriptome sequence data from a papillary thyroid carcinoma tumor patient

  Genome and transcriptome sequence data from a papillary thyroid carcinoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015276

• Genome and transcriptome sequence data from a multifocal glioblastoma multiforme tumor patient

  Genome and transcriptome sequence data from a multifocal glioblastoma multiforme patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015281

• RNA-sequencing of ex vivo exhausted human antigen-specific T cells

  Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. To explore new pathways for reinvigoration of anti-tumor immune functions, we developed a human ex vivo exhaustion model by repetitive antigenic stimulation of primary CD8 T cells. This results in T cells that resemble patient-derived T cells in tumors on a phenotypic and transcriptional level.

  Study EGAS00001006794

• Tumor Thrombus Dataset

  the dataset contains Exome and RNA fastq files of Renal Cell Carcinoma patients, which belongs to "Integrated genomic analysis of tumor thrombus"/

  Dataset EGAD00001008010

• Orthotopic murine Group 3 medulloblastoma in C57Bl/6 mice treated with sham or craniospinal irradiation

  Mice with medulloblastoma (Group 3) were treated with sham (isofluorane and imaging xray) or CSI as described by Abbas et al (2022). Total RNA was isolated with RNeasy Plus Mini Kit (Qiagen), library preparation (SureSelect, Agilent), rRNA depletion (Ribo-Zero Plus, Illumina) and sequencing were carried out by GenomicsWA or Australian Genome Research Facility. Libraries were sequenced on NovaSeq 6000 S1 flow cells as paired-end 150bp reads (Illumina).

  Dataset EGAD00001008510

• Single cell and whole tissue transcriptomes investigating Barrett's oesophagus

  Data consists of 4,640 RNA-sequencing sample libraries. These libraries were sequenced from four sites of the upper gastro-intestinal tract (Barrett’s oesophagus, proximal normal oesophagus, proximal normal stomach, and duodenum) in two experiments. 4,587 libraries were produced in the first experiment in which whole transcriptomes were isolated single cells dissociated from endoscopic biopsy tissue obtained from the four previously mentioned tissues. The other 53 libraries were produced in the second experiment in which whole transcriptomes were isolated from whole tissue from endoscopic biopsies of the four previously mentioned tissues. The data found here are stored in the raw fastq file format from paired end sequencing.

  Dataset EGAD00001004344

• CSER: Clinical Implementation of Carrier Testing Using Next Generation Sequencing (NextGen)

  We will investigate the clinical implementation of genome sequencing (GS) for carrier screening to aid reproductive decision-making in adults. The study is organized into three inter-related Projects. The study population will include women and their partners who receive pre-conception testing. In Project 1, we will conduct a Randomized Clinical Trial to test clinical implementation of WGS compared with usual care. We will integrate WGS results with the electronic medical record (EMR), and measure outcomes from patient and physician perspectives. In Project 2, we will perform whole genome sequencing, including validation and interpretation of the identified variants to identify "actionable variants", meaning variants deemed worthy of reporting. This will include a robust approach using a Return of Results Committee (RORC) for determination of reportable results. In Project 3, we will evaluate the ethical and psychosocial implications of expanded carrier screening using WGS for the return of carrier status and secondary findings, and measure the impact on downstream healthcare utilization and cost. Two groups of women are identified through the electronic medical record. The first group has a clinical carrier screening test, usually Cystic Fibrosis (CF), ordered and completed as part of a preconception planning visit. The second group has a carrier screening test, usually CF, performed during pregnancy, they have delivered their baby and are planning a future pregnancy. Eligible women are randomized to either usual care or genome sequencing (GS). Women randomized into the usual care arm have already received their clinical genetic test. These women will not receive genome sequencing. Women in the GS arm will receive their carrier status results for about 700 gene/condition pairs approximately three months after randomization. If there are results to return, women come in for a genetic counseling session. If there are no results, a letter is sent in the mail. Incidental findings (IF) are returned about one month later. As with the carrier status results, all IF are returned in person, and if there are no results a letter is sent in the mail. If a participant is found to be a carrier of an autosomal recessive condition, her male partner is then eligible and invited to participate in the study and receive GS.

  Study phs000927

• Exome sequencing of early and late passage Patient Derived Xenogratf Tumoroids with matched Patient Derived Xenogratfs and matched normal liver

  The breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, the setting where experimental therapies are typically tested. XENTURION is a unique open-science resource that combines a platform of 129 PDX models and a sister platform of 129 matched PDX-derived tumoroids (PDXTs) from patients with metastatic CRC, with accompanying multidimensional molecular and therapeutic characterization. In this specific dataset we focused our attention on early (passage 3) and late (passage 8-12) PDXTs with their matched PDXs and normal liver

  Dataset EGAD50000000266

• Acral melanoma targeted exome sequencing study (UCSF)

  Acral melanoma affects world populations irrespective of skin color. It has comparatively few single nucleotide mutations, but exhibits genomic instability characterized by structural rearrangements and amplifications. As acral melanoma harbors BRAF (GeneID:673) mutations at low frequencies, we searched for alternative therapeutic targets. We performed targeted deep sequencing of cancer-related genes on 37 acral melanomas and identified point mutations, structural rearrangements and copy number alterations.

  Study phs001596

• cfDNA methylation profiling on longitudinally collected blood plasma of patients with esophageal adenocarcinoma

  Esophageal adenocarcinoma (EAC) is an aggressive cancer characterized by a high risk of relapse post-surgery. Analyzing cell-free DNA (cfDNA) from blood plasma emerges as a promising avenue for therapy response monitoring. This study aims to evaluate the cost-effective and genome-wide cell-free reduced representation bisulfite sequencing (cfRRBS) method combined with computational deconvolution for effective disease monitoring in EAC patients.

  Study EGAS50000000514

• Transcriptomic insights into IPMN-associated PDAC progression

  This study investigates the transcriptomic heterogeneity and evolutionary progression of intraductal papillary mucinous neoplasms (IPMNs) and their associated pancreatic ductal adenocarcinomas (PDAC). Multi-region tumour sampling was performed to characterise spatial variation in gene expression and to identify transcriptional changes associated with malignant transformation. The project aims to improve understanding of tumour evolution in pancreatic cancer and to identify molecular pathways involved in IPMN-to-PDAC progression.

  Study EGAS50000001540

• High-depth whole genome sequencing of paired ductal carcinoma in-situ (DCIS) and germline control samples from 51 individuals.

  Deposited here are whole-genome sequencing data for 51 paired breast cancer DCIS and matched-normal samples taken from the same individual. Average sequence depth is 110x for DCIS samples and 39x for matched-normals. Matched-normals are from blood (n=14) or adjacent normal breast (n=37). Sequencing was performed on Illumina HIseqX (n=70) or Illumina Novoseq (n=32). They are a part of a broader project that uses high-depth WGS to investigate the somatic mutation genomic landscape of DCIS in order to uncover biological insights into breast cancer progression as well as possible methods to stratify DCIS patients for individualised therapy or disease monitoring.

  Dataset EGAD50000002071

• Prospective high-throughput genome profiling in advanced cancers:

  Genomics-based tumor profiling in advanced cancers (aC) was recently demonstrated as feasible in clinical practice. After the prospective pilot PANDORA study done on advanced breast cancers, we conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy

  Study EGAS00001004554

• DNA sequencing for human normal endometrial glands

  To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we conducted whole-exome and whole-genome sequencing for 56 endometrial glands and matched blood samples from 4 women. By collecting endometrial glands from different parts of the endometrium, we showed that multiple glands with the same somatic mutations occupied substantial areas of the endometrium.

  Study EGAS00001005822

• Epigenetic analyses of methylation and nucleosome occupancy in cell-free DNA (cfNOMe)

  Cell-free DNA (cfDNA) has become essential in cancer diagnostics and prenatal testing. We investigate enzymatic cytosine conversion for epigenetic analyses of cfDNA and find that it reliably measures cytosine methylation and nucleosome occupancy. Whereas previously, separate experiments had to be performed to study either epigenetic marking, this approach delivers reliable results for both, enabling more comprehensive and inexpensive epigenetic profiling of cfDNA.

  Study EGAS00001004370

• MutWP5: CRUK Mutographs of Cancer: Lung: PD38234 (Targeted) (2020-01-29)

  Sequencing of LCM-derived microbiopsies from explanted lung from pulmonary fibrosis patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs. . This dataset contains all the data available for this study on 2020-01-29.

  Dataset EGAD00001005925

• Evolutionary trajectories and clonal migration underlying tumor progression and lymph node metastasis in resectable lung cancer

  In this prospective study, targeted deep sequencing was performed on a total of 160 primary tumors (474 regions) and 112 lymph nodes from 125 patients with stage I-III lung cancer (LuCaTH). Progressive evolution at clonal divergence scale was observed while specific driver events were positively selected for clonal sweeps during tumor development. Between-region genetic divergence (BRGD) of tumors were assessed and positively correlated with tumor differentiation. A machine learning algorithm was employed to evaluate clinicopathological and molecular parameters of primary tumors underlying lymph node metastasis. By analyzing clonal lineages and metastatic trajectories across multiple nodal stations, we unraveled a common sequential LNM seeding pattern but with divergent modes of clonal spread.

  Dataset EGAD00001007587

• MutWP5: CRUK Mutographs of Cancer: Lung: PD37920 (Targeted) (2021-02-02)

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs. . This dataset contains all the data available for this study on 2021-02-02.

  Dataset EGAD00001006929

• Lung cancer and non-cancerous plasma cfDNA samples

  The dataset contains 90 lung cancer and 5 non-cancerous lung lesion plasma cfDNA samples collected in EDTA blood collection tubes. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001008666

• Colorectal cancer organoid-stroma biobank cohort

  In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived tumor organoids (PDTOs) show enormous potential for preclinical testing, however, purely epithelial cultures features including the ‘consensus molecular subtypes’ (CMS) are largely eradicated. To better reflect the cell type heterogeneity, we established the CRC organoid-stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAFs) from 30 patients. Whole exome sequencing and transcriptome analysis in various in vitro and in vivo contexts was performed to study the influence of the TME on the CRC phenotype.

  Dataset EGAD00001011173

• Somatic Mutation in Normal Bladder Study

  Adult human somatic tissues are landscapes of mutant clones, but little is known about how these landscapes are shaped by known cancer risk factors. The goal of this study was to determine how the main bladder cancer risk factors (sex and smoking) change the mutational landscape of the normal urothelium. We collected normal urothelium from 45 donors at autopsy by brushing ~2cm² of the surface epithelium in the upper part (dome) and lower part (trigone) of the bladder (79 samples total). To identify mutations with high sensitivity we employed ultradeep (~5000x) DNA error-correcting duplex-sequencing on a panel of 15 protein coding genes and the TERT promoter, previously described to be under positive selection in normal urothelium or relevant to bladder cancer. We identified thousands of clonal driver mutations, which demonstrate pervasive positive selection in the normal urothelium. Males showed a significantly higher number of driver truncating mutations in RBM10, CDKN1A and ARID1A, despite similar rates of non-coding mutations, indicating stronger positive selection and clonal expansion in the male urothelium. We also discovered clonal expansions driven by activating TERT promoter mutations in the normal bladder, which were strongly associated with age and smoking. These results demonstrate that sex and smoking shape the clonal landscape of the normal bladder and indicate that the high mutational content of normal tissues might be leveraged to study the effect of mutations in vivo (i.e. natural saturation mutagenesis). We will deposit in dbGaP de-identified relevant clinical information from the 45 donors and the fastq files derived from duplex sequencing of the 79 samples in the study. We will also deposit fastq files derived from duplex sequencing of 3 control cord blood samples.

  Study phs004105

• Oncogenic Ectodomain deletion of FGFR1 caused by Breakage-Fusion-Bridges in Squamous Cell lung Cancer

  The identification of recurrent 8p11.23 amplifications including FGFR1 raised the hope of a treatable target in squamous cell lung cancer (SQLC). However, only a minority of patients with FGFR1-amplified tumors respond to single agent inhibitor therapy targeting FGFR. To understand the underlying mechanism of FGFR1 dependency, we performed whole genome and transcriptome sequencing of 25 FGFR1-amplified primary tumors with unknown response upon FGFR inhibition. In addition, we performed deep sequencing of 26 FGFR1-amplified samples whereof the response upon FGFR inhibition was known for 25 samples. In both cohorts we identified intra-chromosomal tail-to-tail breaks close to the FGFR1 transcription start site, being responsible for focal amplification of FGFR1. These specific breaks are caused by a Breakage-Fusion-Bridge-like (BFB-like) mechanism. Here, we associate these breaks with FGFR inhibitor sensitivity. Moreover, in some cases these breaks are located within the open reading frame of FGFR1, which leads to the expression of an ΔEC-FGFR1 transcript that lacks the ecto-domain. Overexpression of ΔEC-FGFR1 transforms Baf3 cells and lead to an FGFR1-dependent phenotype. Our results demonstrate that the truncation of the FGFR1 ectodomain is a frequent event in 8p11.23-amplified squamous cell lung cancer caused by tail-to-tail breaks. These breaks might be used as a predictive therapeutic marker to stratify patients for FGFR-inhibitor therapy.

  Study EGAS00001005059

• Multimodal plasma and urinary cell-free DNA profiling improves risk stratification in newly diagnosed prostate cancer

  Prostate cancer (PCa) is a heterogeneous disease, impeding early detection and risk stratification. Liquid biopsies (LBx) enable minimally invasive tumor profiling, but circulating tumor-derived DNA (ctDNA) detection remains difficult, particularly in early-stage PCa. We developed a multimodal LBx approach combining genomic and epigenomic cell-free DNA (cfDNA) features in plasma and urine from newly diagnosed PCa patients to improve early characterization of PCa and risk stratification of aggressive disease. Plasma and urine samples from 55 localized PCa (lPCa) patients, 18 advanced PCa (aPCa) patients, and 36 cancer-free controls were subjected to low-coverage whole-genome sequencing and methylated DNA immunoprecipitation sequencing to assess fragmentation, chromosomal instability, and methylation in cfDNA. This complementary approach yielded a 45% ctDNA detection rate in newly diagnosed PCa. Major differences were observed between aPCa and controls, reflecting increasing signals with tumor progression. Epigenomic cfDNA features differentiated lPCa from aPCa, and ctDNA was detected in 46% of PCa patients with prostate-specific antigen <10 ng/ml, suggesting potential for risk stratification. This study highlights the value of multimodal LBx approaches for early characterization of primary PCa and identification of aggressive disease at initial diagnosis. Integration into clinical workflows could complement diagnostics and support personalized decision-making tailored to patients’ PCa risk profiles. 

  Study EGAS00001008195

• Whole genome sequencing of matched primary and metastatic acral melanomas

  Next generation sequencing has enabled systematic discovery of mutational spectra in cancer samples. Here we used whole genome sequencing to characterise somatic mutations and structural variation in a primary acral melanoma and its lymph node metastasis. Our data show that the somatic mutational rates in this acral melanoma sample pair was more comparable to the rate reported in cancer genomes not associated with mutagenic exposure than in the genome of a melanoma cell line or the transcriptome of melanoma short-term cultures. Despite the perception that acral skin is sun-protected, the dominant mutational signature in these samples is compatible with damage due to ultraviolet light exposure. A nonsense mutation in ERCC5 discovered in both the primary and metastatic tumours, could also have contributed to the mutational signature through accumulation of unrepaired dipyrimidine lesions. However, evidence of transcription-coupled repair was suggested by the lower mutational rate in the transcribed regions and expressed genes. The primary and the metastasis are highly similar at the level of global gene copy number alterations, loss of heterozygosity and single nucleotide variation (SNV). Furthermore, the majority of the SNVs in the primary tumour were propagated in the metastasis and one non-synonymous coding SNV and one splice site mutation appeared to arise de novo in the metastatic lesion.

  Study EGAS00001000169

• Similarity and diversity of the tumor microenvironment in multiple metastases: critical implications for overall and progression-free survival of high-grade serous ovarian cancer.

  The tumor microenvironment is pivotal in influencing cancer progression and metastasis. Different cells co-exist with high spatial diversity within a patient, yet their combinatorial effects are poorly understood. We investigate the similarity of the tumor microenvironment of 192 local metastatic lesions in 61 ovarian cancer patients. An ecologically inspired measure of microenvironmental diversity derived from multiple metastasis sites is correlated with clinicopathological characteristics and prognostic outcome. We demonstrate a high accuracy of our automated analysis across multiple sites. A low level of similarity in microenvironmental composition is observed between ovary tumor and corresponding local metastases (stromal ratio r = 0.30, lymphocyte ratio r = 0.37). We identify a new measure of microenvironmental diversity derived from Shannon entropy that is highly predictive of poor overall (p = 0.002, HR = 3.18, 95% CI = 1.51-6.68) and progression-free survival (p = 0.0036, HR = 2.83, 95% CI = 1.41-5.7), independent of and stronger than clinical variables, subtype stratifications based on single cell types alone and number of sites. Although stromal influence in ovary tumors is known to have significant clinical implications, our findings reveal an even stronger impact orchestrated by diverse cell types. Quantitative histology-based measures can further enable objective selection of patients who are in urgent need of new therapeutic strategies such as combinatorial treatments targeting heterogeneous tumor microenvironment.

  Study EGAS00001002065

• Cell of Origin and Early Evolution of Leukemia in Down Syndrome

  To investigate the mechanism by which GATA1s and STAG2 deficiency contribute to Down Syndrome leukemogenesis, specifically within the propagating CD34/CD117 cell fractions from primary xenografts, we carried out transcriptional and epigenetic profiling by RNAseq and ATACseq. The chromatin accessibility landscape was compared to bulk ATACseq of individually sorted N-FL HSPC subpopulations. To investigate the mechanism underlying the synergy between T21 and GATA1s in driving preleukemia development, we analyzed the binding occupancy of GATA1. We performed Cut&Run assays to profile genome-wide GATA1 binding sites and also to quantify binding changes upon GATA1s editing in N-FL and T21-FL CD34+ enriched HSPCs. Lastly, we profiled miRNAs from N-FL and T21-FL CD34+ enriched HSPCs by miRNA-Seq.

  Dataset EGAD00001006555

• Anaplastic Oligodendroglioma AO Exome-seq data

  Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. 80% of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frame shift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumor type. Our analysis provides further insights into the unique and shared pathways driving AO.

  Dataset EGAD00001001452

• SPECIAL: scRNA-seq

  Tumour biopsies were collected from twenty-three patients (46 samples) (of which 20 were matched) with locally advanced or metastatic melanoma (stage IIIB – stage IV). Library construction was done either with the Chromium Single Cell 3ʹ GEM, Library & Gel Bead Kit v3 (n = 16; 10x genomics, Cat#1000092) or the Chromium Single Cell A Chip Kit and 5’ Library & Gel Bead Kit (10x genomics, Cat#1000014). All libraries were sequenced on Illumina NextSeq, HiSeq4000 or NovaSeq6000 until sufficient saturation was reached (60% on average). The reference genome used in this study was GRCh38.

  Dataset EGAD00001009291

• Single-cell antibody-derived tag sequencing data of peripheral blood mononuclear cells obtained from 30 ATL patients, 11 HTLV-1-infected asymptomatic carriers, and 4 healthy donors.

  Single-cell antibody-derived tag sequencing (scADT-seq) data of peripheral blood mononuclear cells (PBMCs) obtained from 30 ATL patients (34 samples including 4 sequential ones), 11 HTLV-1-infected asymptomatic carriers, and 4 healthy donors.

  Dataset EGAD00001007017

• Genome wide association study for early onset coronary disease and related phenotypes (ADVANCE)

  ADVANCE (Atherosclerotic Disease, VAscular functioN, and genetiC Epidemiology) is a large epidemiological study of genetic and non-genetic determinants of coronary artery disease (CAD) that started in 2000 as a collaborative effort between researchers at Stanford University and Kaiser Permanente of Northern California. The overarching goal of the study is to improve our ability to prevent, diagnose and treat CAD. The initial study included recruitment of over 3600 subjects (including 1873 subjects with incident clinically significant coronary disease and 1745 control subjects) from multiple race/ethnic backgrounds. A subset of ~ 500 subjects with very early onset coronary disease (men < 45 and women < 55) and ~ 500 similar aged controls were genotyped using the Illumina 550K platform as part of an NIH funded effort within the STAMPEED consortium.

  Study phs000423

• NIDDK⁄CIDR Inflammatory Bowel Disease Genetics Consortium (IBDGC) Genome Wide Association Study in Familial Crohn's Disease

  The National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium (NIDDK - IBDGC) conducted a genome wide association study (GWAS) using the Human Omni2.5-Quad beadchip from Illumina to identify disease variants associated with familial Crohn's disease. This study includes a subset of individuals from an original cohort of affected subjects and affected/unaffected relatives from a previous linkage scan which showed increased linkage evidence at three novel risk loci. A total of 708 samples were selected based on various criteria for inclusion from the 6 Genetic Research Centers (GRC) in North America that participate in the IBDGC. This project was supported by an ancillary R01 grant from the NIDDK with resources made available through the IBDGC.

  Study phs000367

• GWAS in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

  The study comprises SLE patients recruited from specialist rheumatology clinics from the United States, Mexico, Argentina, Chile and Peru. Two strategies were used to enrich samples for Native American ancestry: a. previously genotyped Hispanic and Latin American and US Native American individuals were selected according to their ancestry based on 253 ancestry informative markers as part of the Lupus Large Association 2 Study. The approximate 35% of the samples were primarily of European and Native American admixture was selected; b. the recruitment of patients took place primarily in countries with little African admixture. All samples were genotyped on the HumanOmni1-Quad BeadChip using manifest H at the Oklahoma Medical Research Foundation. The Illumina clustering algorithm with GenomeStudio v2011.1 was used.

  Study phs001025

• Clinical Outcomes and ctDNA Correlates for CAPOX BETR: A phase II trial of Capecitabine, Oxaliplatin, Bevacizumab, Trastuzumab in Previously Untreated Advanced HER2+ Gastroesophageal Adenocarcinoma

  We performed circulating tumor DNA (ctDNA) analysis on plasma of patients with advanced HER2 positive gastroesophageal adenocarcinomas who were treated on a phase 2 clinical trial testing the addition of bevacizumab to capecitabine, oxaliplatin, and trastuzumab. ctDNA was analyzed using panel based next generation sequencing assay (Predicine CARE), low-pass whole genome sequencing (LP-WGS), and methylation based panel assay (Predicine ALERT). This allowed us to derive tumor mutational profiles, circulating tumor fractions in plasma, and changes in both over time. We show that tumor fraction and the presence of mutations in the MAPK pathway are prognostic in our patient cohort. LP-WGS data from baseline and cycle 2 of treatment is available through dbGaP. Additional data is submitted alongside the manuscript.

  Study phs003706

• Tracking Therapy-Resistant Alterations in Childhood Acute Lymphoblastic Leukemia

  Relapse is currently the major cause of death in children with B-ALL. The goal of this study is to uncover the genetic underpinnings of relapsed B-ALL in the AALL1331 cohort (PMID: 33651090) via whole genome and transcriptome sequencing of matched diagnosis, relapse, and remission specimens. We aim to discover genetic alterations that drive treatment resistance in relapsed tumors. We also aim to investigate the feasibility of detecting residual tumors from remission samples with the ultimate goal to improve risk stratification using NGS-based minimal residual disease (MRD) detection. Here we only report data from patients in remission with the aim of determining MRD. We will submit corresponding data for the diagnosis and relapse components of our cohort in a future version of our study.

  Study phs003409

• 3.5KJPNv2, an allele frequency panel of 3,552 Japanese individuals

  In the Tohoku Medical Megabank Project, we have conducted whole-genome sequencing of nearly 4,000 individuals from a Japanese population, and constructed an allele frequency panel of 3,552 individuals (3.5KJPNv2) after removing genetically related individuals. The 3.5KJPNv2 was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. The 3.5KJPNv2 includes variants in chromosome X and mitochondrial genome as well as autosome. The submitter has changed the access level of this study from controlled-access [Type I] to un-restricted access since 11th, January, 2019. The un-restricted access data ?hum0015.v3.3.5kjpnv2.v1? are available at the NBDC site: https://humandbs.biosciencedbc.jp/en/hum0015-v3. This study does not contain any controlled-access dataset.

  Study JGAS000159

• A sequence-based genetic dissection of human immune cell types and implications for immune-related disease.

  The immune system is an intricate biological network mediating interactions with other organisms while preserving the integrity of our tissues. By mounting appropriate responses it protects us from a vast range of pathogens while inadvertent immune system attacks on self result in autoimmune diseases. The project aims to discover whether and to what extent the behaviour of the immune system is genetically regulated and to detect the relationships of diverse immune cells with autoimmunity. The project consists of the genetic analysis using up to ~8.2 Million variants, deriving from high density genotyping data and low pass whole genome sequencing, and quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages belonging to the SardiNIA/ProgeNIA study.

  Study EGAS00001000574

• Cross-species genomics identifies TAF12, NFYC and RAD54L as novel choroid plexus carcinoma oncogenes

  Choroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options. Using a new mouse model of the disease and a large cohort of human CPCs, we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain. TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice. TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair. Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy.

  Study EGAS00001000961

• ICGC PedBrain: Deep-sequencing of childhood brain tumors.

  Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.

  Study EGAS00001000215

• Relaxed selection during a recent human expansion

  To better understand and quantify the effect of a recent expansion process on the amount and pattern of mutation load, we screened the ascending genealogies of 3916 individuals from the CARTaGENE cohort (Awadalla et al. 2013) that were linked to the BALSAC genealogical database (http://balsac.uqac.ca/). Using stringent criteria on the quality of genealogical information, we selected (front) individuals whose ancestors were as close as possible to the front of the colonization of Quebec, and (core) individuals whose ancestors were as far as possible from the front. We then sequenced these 102 individuals at very high coverage (mean 89.5X, range 67X-128X) for 106.5 Mb of exomic and UTR regions and contrasted their genomic diversity to detect if sites with various degrees of conservation and deleteriousness had been differentially impacted by selection.

  Study EGAS00001001957

• Mullighan - PAX5-driven Subtypes

  Using integrated genomic analysis of 1.988 childhood and adult cases, we describe a revised taxonomy of B-cell acute lymphoblastic leukemia, which incorporates 23 subtypes defined by chromosomal rearrangements, sequence mutations, or heterogeneous genomic alterations. Two subtypes have frequent alterations of the B lymphoid transcription factor gene PAX5. One, PAX5alt, has diverse PAX5 alterations, and a second subtype is defined by a single mutation, PAX5 P80R. We show that P80R impairs B lymphoid development and promotes the development of B-ALL in vivo. These results demonstrate the utility of transcriptome sequencing to classify B-ALL and reinforce the central role of PAX5 as a checkpoint in B lymphoid maturation and leukemogenesis.

  Study EGAS00001003266

• Single cell whole genome sequencing of high hyperdiploid acute lymphoblastic leukemia

  This dataset was collected from viable bone marrow cells obtained at diagnosis from nine patients with high hyperdiploid ALL and one normal bone marrow sample. All samples were subjected to low pass single cell whole genome sequencing with the median sequencing coverage of 0.02x. Single nuclei in G0/G1 phase were isolated using a fluorescence-activated cell sorting (FACS) cytometer. DNA libraries were constructed and associated next-generation sequencing was carried out by European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Further details regarding the DNA libraries construction are available by Bos et. al., 2019 (https://link.springer.com/protocol/10.1007/978-1-4939-8931-7_15). The dataset has been used for copy number aberrations analysis.

  Study EGAS00001006347

• Genomic Landscape and Clonal Architecture in Pediatric Myeloid Neoplasms with Chromosome 7 Deletions

  Full and partial loss of chromosome 7 (del7, 7q-) are prevalent cytogenetic abnormalities in pediatric myeloid neoplasms resulting in haploinsufficiency of key hematopoietic regulators on chromosome 7. While the genomic landscape of myeloid neoplasms in adults with del7 and 7q- has been described, pediatric patients with similar chromosome 7 losses have not been compiled into a single, comprehensive study utilizing modern sequencing strategies. To this end, we assembled a cohort of 108 pediatric and young adult patients representing a mixture of diagnoses. Using WGS, WES, and RNAseq, we compared the co-occurring mutations and gene expression levels in our cohort to those found in pediatric and young adult patients with two intact copies of chromosome 7. We also performed single-cell multi-omics on a subset of eight samples.

  Study EGAS00001008055

• Evolutionary landscape of clonal hematopoiesis in 3359 individuals from the general population

  This project contains longitudinal data for processed somatic variant calls and data on core phenotypic variables for 3359 community-based individuals ≥60 years, a sub-cohort of the population-based Lifelines cohort (167,729 participants). Cases with peripheral blood count abnormalities and population-based controls were included. Next-generation sequencing data were generated with a median time period of 43 months between baseline and follow-up visit. For 327 individuals a third visit sample was included. Error-corrected sequencing was performed using single-molecule tagged molecular inversion probes targeting 27 myeloid and lymphoid driver genes. The threshold for variant calling was set at ≥1% VAF and ≥10 consensus variant reads. Details on sample selection, sequencing technique, variant calling procedures and data curation are described (van Zeventer et al. 2023).

  Study EGAS00001007087

• Genome-wide associations of human gut microbiota variation and implications for causal inference analyses

  Here we use appropriate taxon-specific models along with support from independent cohorts to show association between human host genotype and gut microbiome variation. Using fecal derived 16S rRNA gene sequences and host genotype data from the Flemish Gut Flora Project (FGFP) we identify genetic associations involving multiple microbial traits. Mendelian randomization analysis was able to estimate associations between microbial traits and disease, however in the absence of clear microbiome driven effects, caution is needed in interpretation. This work marks a growing catalog of genetic associations which will provide insight into the contribution of host genotype to gut microbiome. Despite this, the uncertain origin of association signals will likely complicate future work looking to dissect function or use associations for causal inference analysis.

  Study EGAS00001004420

• Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

  No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

  Study EGAS50000000211

• Whole Exome Sequencing of Pancreatic Neuroendocrine Tumors at The Human Genome Sequencing Center, Baylor College of Medicine (HGSC-BCM)

  Pancreatic neuroendocrine tumors (PNETs), often referred to as "islet cell tumors", are neuroendocrine neoplasms that arise from cells of the endocrine and nervous system within the pancreas. These rare tumors which originate from the pancreatic islet are divided into many categories and are often classified by the hormone most strongly secreted. With the collaboration of the Elkins Pancreatic Center, the Human Genome Sequencing Center (HGSC) at Baylor College of Medicine had access to approximately 30 untreated tumor specimens and matched normal blood samples. Since the onset and progression of cancer is driven by extensive mutation of the genome, we are combining enrichment of exonic DNA with next generation sequencing to detect and characterize the somatic mutation profile of patients with pancreatic neuroendocrine cancer. This work was done at the Human Genome Sequencing Center (HGSC) in collaboration with the Elkins Pancreatic Center at Baylor College of Medicine in Houston, TX and was supported by grant number 5U54HG003273 from National Human Genome Research Institute (NHGRI).

  Study phs000871

• International Cancer Proteogenomics Consortium (ICPC): Proteogenomics of East-Asian Breast Cancer

  The incidence of invasive breast cancer is rapidly increasing in East Asia, enriching in younger patients and luminal disease. We presented a deep proteogenomic landscape of a prospectively enrolled early-stage cohort in Taiwan to uncover the etiology, age-related subtype and oncogenic vulnerabilities underlying the heterogeneous disease. Multilayer proteogenomic architecture revealed distinct endogenous and environmental carcinogen-associated mutagenesis, linking APOBEC (apolipoprotein-B mRNA editing enzyme, catalytic polypeptide-like) cytidine deaminase and DBAC (dibenz[a,j] acridine) signatures to significantly elevated hormone biosynthesis and chemical carcinogenesis in younger patients, and identifying a novel subset of high mutation burden and immune escape potentially beneficial from combined epigenetic therapy and immunotherapy. A proteomics-informed classification resolves luminal heterogeneity, defines high-risk recurrent luminal disease and nominates biomarkers and actionable druggable pathways. Furthermore, proteogenomics profile distinguished a young luminal population susceptible to exogenous carcinogen and having DNA repair deficiency. This study illuminates the age-related molecular subtypes and oncogenic vulnerabilities, providing a proteogenomics-transformative guide for patient stratification and precision therapeutics beyond clinical staging.

  Study phs003150

• A Multi-Gene Mutation Classification of 468 Colorectal Cancers Reveals a Prognostic Role for APC

  Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinic-pathologic staging for decades. There is a need to molecularly stratify subpopulations of CRC to better predict outcome and assign therapies. Here we report targeted exome sequencing of 1,321 cancer-related genes on 468 tumor specimens, which identified a subset of 17 genes that best classify CRC, with APC (Gene ID: 324) playing a central role in predicting overall survival. APC may assume 0, 1, or 2 truncating mutations, each with a striking differential impact on survival. Tumors lacking any APC mutation carry a worse prognosis than single APC mutation tumors, but tumors with two APC mutations and KRAS (Gene ID: 3845) and TP53 (Gene ID: 7157) mutations confer the poorest survival among all the subgroups examined. Our study demonstrates a substantial prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC.

  Study phs001111

• Genome-wide mutational consequences of nucleotide excision repair-deficiency through XPC deletion in a human adult stem cell culture

  Nucleotide excision repair (NER) is one of the main DNA repair pathways that protect cells against genomic damage. Deficiency in this pathway can contribute to the development of cancer and accelerate aging. NER-deficiency is an important determinant for cancer treatment outcome, as NER-deficient tumors are selectively sensitive to cisplatin treatment. While NER-deficiency has been linked to mutational Signature 5, not all NER-deficient tumors are characterized by a high Signature 5 contribution, illustrating the importance to further characterize the mutational consequences of NER-deficiency. Here, we analyzed the mutational profile of a human adult stem cell (organoid) culture that is deficient in NER through XPC deletion by CRISPR-Cas9 gene-editing, and subsequent whole-genome sequencing analysis of a clonally derived organoid. We found that XPC deletion results in an increase in base substitution load and specifically induces Signature 8 mutations, a mutational signature with previously unknown etiology. Presence of Signature 8 may, therefore, serve as a novel biomarker for NER-deficient tumors and could improve personalized treatment strategies.

  Study EGAS00001002681

• Primary prostate Hi-C

  Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. Despite large-scale tumour sequencing efforts, the impact of mutations on the genetic architecture in cancer remains ill-defined due to limited integration of genomics data across dimensions. We addressed this limitation by assessing the impact of structural variants on the chromatin states and the three-dimensional organization across benign and malignant primary prostate genomes. We find high concordance in the three-dimensional genome organization between malignant and benign prostate tissues, arguing for constraints to the three-dimensional genome of prostate tumours. Moreover, we identify structural variants as effectors of changes to focal chromatin interactions, guiding cis-regulatory element hijacking that imposes opposing expression changes on genes found at antipodes of a rearrangement. This leads to the repression of tumour suppressor gene expression and up-regulation of oncogenes, such as at the TMPRSS2-ERG and PMEPA1-ZNF156 loci. Collectively, our results argue that cis-regulatory element hijacking by structural variants overshadows large-scale topological changes to alter gene regulation and promote oncogenesis.

  Study EGAS00001005014

• Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones

  The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyzed tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we were able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identified several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Strikingly, certain cell populations present before treatment exhibited gene expression profiles that matched those of resistant tumor cell clusters, present after treatment. We confirmed that these clusters were resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrated that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identified differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors.

  Study EGAS00001006113

• Functional screening on patient-derived organoids identifies a therapeutic bispecific antibody that triggers EGFR degradation in LGR5+ tumor cells

  Patient-derived organoids (PDOs) have demonstrated predictive value in prospective clinical trials supporting selection of personalized treatments. Because PDOs retain the organization and physiological functions of their source tissue, PDO biobanks could also be an ideal substrate to screen for novel therapeutic interventions. Here we describe a large-scale functional screen of dual targeting bispecific antibodies (bAbs) on a colorectal cancer (CRC) PDO biobank to target their dependency on cancer stem cells. A novel drug discovery pipeline was assembled where therapeutic bAb panels generated against WNT and receptor tyrosine kinases (RTK) targets were functionally evaluated by high content imaging to capture the complexity of PDO responses across a wide range of different CRCs and paired normal colonic mucosa samples. Our strategy resulted in a bAb that specifically triggers EGFR degradation in LGR5+ CSCs and that exhibits unique therapeutic properties such as potent growth inhibition of KRAS mutant CRCs, blockade of metastasis initiation in preclinical models and minimal toxicity towards normal LGR5+ colon stem cells.

  Study EGAS00001004584

• The miR-185/PAK6 Axis Predicts Therapy Response and Regulates Survival of Drug-Resistant Leukemic Stem Cells in Chronic Myeloid Leukemia

  Overcoming drug resistance and targeting cancer stem cells remain challenges for curative cancer treatment. To investigate the role of miRNAs in regulating drug resistance and leukemic stem cell (LSCs) fate, we performed global transcriptome profiling in treatment-naïve chronic myeloid leukemia (CML) stem/progenitor cells and identified that miR-185 levels anticipate their response to ABL tyrosine kinase inhibitors (TKIs). miR-185 functions as a tumor suppressor; its restored expression impaired survival of drug-resistant cells, sensitized them to TKIs in vitro, and markedly eliminated long-term repopulating LSCs and infiltrating blast cells, conferring a survival advantage in pre-clinical xenotransplantation models. Integrative analysis with mRNA profiles uncovered PAK6 as a crucial target of miR-185 and pharmacological inhibition of PAK6 perturbed the RAS/MAPK pathway and mitochondrial activity, sensitizing therapy-resistant cells to TKIs. Thus, miR-185 presents as a potential predictive biomarker, and dual targeting of miR-185-mediated PAK6 activity and BCR-ABL may provide a valuable strategy for overcoming drug resistance in patients.

  Study EGAS00001004153

• Advancing fast in the analysis of circulating tumour DNA

  In cancer patients, solid tumours also release DNA fragments into the blood, and they are called Circulating Tumours DNA (ctDNA). Nowadays, the standard procedure for cancer monitoring is analysis of surgically obtained biopsies. They generate a big amount of material, but the operation is highly invasive and provide medical doctors with a single-time snapshot of the tumours, which are often highly changeable. Analysis of ctDNA, on the other hand, can provide continuous information regarding the tumour itself without the need of invasive procedures. This is why interest in this method is growing, and with it, the need for its technological optimization. Guanhua Zhu and colleagues, at the Genome Institute of Singapore, developed a methodology to quantify ctDNA burden, which means to estimate the amount of tumours derived circulating DNA among all cell-free DNA in the blood of individuals. Their work, published in Nature Communications in april 2021 and summarized in a sketch below, uses state-of-the art methods to analyse cfDNA degradation patterns at promoters and exon regions, to discern it from the DNA coming from the tumours. The bright point of their approach is that simultaneously enable for profiling of actionable cancer mutations and quantitative estimation of ctDNA burden. Their sequencing data of ctDNA has been deposited in the EGA under the accession number EGAS00001004657. This study sums up to a total of 37 of cfDNA and 36 about ctDNA present up to date in the EGA archive. The existence of cfDNA was firstly described back in 2002, while the use of ctDNA analysis in the oncological field exploded only after 2016. The approach is rapidly evolving, moving in parallel with the ever-improving sequencing technologies. Especially, the possibility to obtain high quality sequences from minimal amount of material is a crucial factor. Being able to alleviate cancer patients of disturbing and often slow-recovery procedures, while at the same time improving the quality of diagnosis and disease monitoring seems like a lot to ask. Thankfully, we are blessed with brilliant and dedicated scientists from all around the world who collaborate to make this a reality, sharing their results, knowledge and data.

  Blog advancing-fast-in-the-analysis-of-circulating-tumour-dna

• MutWP5: CRUK Mutographs of Cancer: Cancer Mastectomy (WG)(Novaseq)

  Sequencing of LCM-derived microbiopsies from 40 women who underwent mastecomies due to breast cancer. LCM and sequencing will be conducted on both normal, unaffected breast, and, where possible, tumour tissue. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue, and compare findings between the normal and associated cancer tissues. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this poriton of the study will be compared to women who had cosmetic breast reduction surgeries and those who are BRCA carriers. . This dataset contains all the data available for this study on 2023-03-08.

  Dataset EGAD00001010114

• Deep whole genome ctDNA chronology of treatment-resistant prostate cancer

  Circulating tumor DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genotyping and longitudinal disease monitoring. We performed deep whole-genome sequencing of serial plasma and synchronous metastases in patients with aggressive prostate cancer. We comprehensively assess all classes of genomic alterations and demonstrate that ctDNA harbors multiple dominant populations whose evolutionary histories frequently indicate whole-genome doubling and shifts in mutational processes. Although tissue and ctDNA showed concordant clonally-expanded cancer driver alterations, each individual metastasis contributed only a minor share of total ctDNA. By comparing serial ctDNA before and after clinical progression on potent androgen receptor (AR) pathway inhibitors, we reveal population restructuring converging solely on AR augmentation as the dominant genomic driver of acquired treatment-resistance. Finally we leverage nucleosome footprints in ctDNA to infer mRNA abundance in synchronously biopsied metastases, including treatment-induced changes in AR pathway transcriptional activity.

  Dataset EGAD00001008460

• 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. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines revealed a unique form of structural variation, termed heterocateny here, characterized by heterogeneous, interrelated, and repetative patterns of concatemerized virus and host DNA segments. Evidence of heterocateny was detected in extrachromosomal and/or intrachromosomal DNA in all cases. Unique breakpoint sequences shared across structurally heterogeneous virus-host concatemers within each cancer facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that unstable virus and virus-host concatemers in ecDNA or integrated form mediate insertion into and excision from chromosomes, capture, rearrangement, and rolling-circle amplification of host DNA, and chromosomal rearrangements. The data indicate that heterocatena is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intra-tumoral heterogeneity and clonal evolution.

  Study EGAS00001006652

• Single cell PDAC samples

  h5 files from 15 single cell PDAC samples described in "Transcription phenotypes of pancreatic cancer are driven by genomic events events during tumour evolution"

  Dataset EGAD00010001811

• The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival

  Transcriptomic sequencing on pre-immunotherapy melanoma patients.

  Dataset EGAD00001007710

• Evolutionary Trajectories of Small Cell Lung Cancer under Therapy

  We performed whole exome sequencing, whole genome sequencing and transcriptome sequencing of multiple tumor regions from 65 patients with SCLC.

  Dataset EGAD50000000243

• Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness

  RNAseq from patient-derived primary tumor cells, cultured or not on organotypic cultures mimicking the tumor microenvironment

  Study EGAS50000000355

• 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

• 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

• Whole genome analysis of liver cancer by long-read sequencing

  Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture

  Study JGAS000361

• ICGC Breast Cancer Project

  A comprehensive characterisation and analysis of human breast cancers through genome-wide approaches including genomics, transcriptomics and epigenomics.

  Study EGAS00001001195

• Mosaic_Colorectal_Metastasis

  A comparison of the somatic variation present in a primary colorectal tumour and three different liver metastases from the same patient.

  Study EGAS00001000613