5522 results for "*oma"

in 82.83 milliseconds.

• DNA methylation at HBV integrants and flanking host genomes

  Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either the human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis.

  Study JGAS000015

• Aberrant (pro)renin receptor expression induces genomic instability by chromatin remodeler SMARCA5 disruption during the pancreatic ductal adenocarcinoma

  The aim of the present study is to elucidate whether aberrant (P)RR expression induces genomic instability in human pancreatic ductal epithelial (HPDE) cells, which are transforming into pancreatic ductal adenocarcinoma (PDAC).

  Study JGAS000143

• RNA-seq analysis of BMP-stimulated glioma initiating cells

  Bone morphogenetic protein (BMP) signaling has been shown to suppress progression of glioblastoma by promoting astrocytic differentiation; however, roles of BMP signaling in cell proliferation and apoptosis of glioblastoma cells remains to be elucidated. We here performed RNA-seq analysis of glioma initiating cells to identify transcriptional target(s) of BMP.

  Study JGAS000077

• Sequencing cancer mutations in various types of lung cancer using the long-read, portable sequencer

  In this study, we used a long-read and portable sequencer MinION to identify cancer mutations in lung adenocarcinoma cells. We performed cDNA amplicon sequencing for various types of mutations such as point mutations in EGFR and KRAS and oncogenic fusion transcripts in ALK and RET. Using the long reads of MinION, we also conducted mutation phasing of EGFR TKI-sensitive and resistant mutations, which would provide useful information to next thrapeutic approaches for cancers. We applied this method to identify mutation genotypes of eight clinical samples from Japanese lung adenocarcinomas. This method could provide new sequencing-based diagnostic approaches for lung cancers. Additinally we also performed cancer mutation identification of risk-dependent unique samples. Usual interstitial pneumonia (UIP) is a risk factor for lung carcinogenesis. This study was performed to characterize mutagenesis and mutational target genes underlying lung carcinogenesis in patients with UIP.We performed whole exome sequencing of lung adenocarcinoma with usual interstitial pneumonia.

  Study JGAS000065

• High-coverage whole exome sequence in non-TRU-type lung adenocarcinomas

  In order to elucidate the key genetic events in non-TRU-type lung cancer, we selected 43 non-TRU-type lung adenocarcinomas and performed a whole exome sequence and RNA-seq analysis using a next-generation sequencer. The results of the analysis identified mutations in TP53, KRAS and NKX2-1 as the top three significantly mutated genes, while the EGFR mutation was rare in this cohort. Eight NKX2-1 mutations (5 frameshift, 2 nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1 mutations (missense and frameshift). All NKX2-1 mutants were transcriptionally inactive in reporter assays. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1 mutations (5 cases), while 1 enteric and 1 acinar adenocarcinoma harbored the NKX2-1 mutation.

  Study JGAS000105

• Genomic subtypes and cellular phenotypes of high-grade endometrial carcinoma

  Based on the mechanism of carcinogenesis, endometrial cancer (EC) is classified into two major types, Type I and Type II. Type I EC is characterized by G1/G2 histology, accounting for about 80% of all uterine carcinomas. On the other hand, Type II EC, which often develops after menopause, is estrogen-independent and consists of serous and clear cell carcinomas. G3 EC is often classified as a Type II EC, but the pathogenesis is thought to be a mixture of estrogen-dependent and estrogen-independent carcinogenesis. We will conduct an integrative genomic analysis to clarify the pathogenesis of Type II EC and redefine its classification by combining genomic status with cell phenotypes reflected in gene expression profiles.

  Study JGAS000753

• Whole exome sequencing of uterine adenomyosis

  Uterine adenomyosis, defined by proliferation of the ectopic endometrial glands in myometrium, is a common benign uterine disorder that significantly impairs the quality of life of the women it affects. Adenomyosis lesions have chronic inflammatory reactions as well as cancer-like features such as invasive capacity into the normal myometrium. In contrast to endometriosis and leiomyoma, the genomic characterization of adenomyosis has yet to be reported. We conducted high-coverage whole exome sequencing analyses of freshly frozen adenomyosis samples, as well as co-occurring leiomyoma. Our WES analyses showed that adenomyosis is a clonal disorder with somatic mutations.

  Study JGAS000169

• Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma

  Myasthenia gravis (MG) is a neurological disease caused by autoantibodies against neuromuscular-associated proteins. While MG is frequently developed in thymoma patients, the etiologic factors for MG are not well understood. Here, by constructing a comprehensive atlas of thymoma using bulk and single-cell RNA-seq, we identified ectopic expression of neuromuscular molecules in MG-associated thymoma (MG-thymoma). These molecules were originated from a distinct subpopulation of medullary thymic epithelial cells (mTECs), which we named neuromuscular mTECs (nmTECs). MG-thymoma also exhibited microenvironments dedicated to autoantibody production, including ectopic germinal center formation, T follicular helper cell accumulation, and type 2 conventional dendritic cell migration. Cell-cell interaction analysis also predicted the interaction between nmTECs and T/B cells via CXCL12-CXCR4. The enrichment of nmTECs presenting neuromuscular molecules within MG-thymoma was further confirmed by immunohistochemically and by cellular composition estimation from MG-thymoma transcriptome. Altogether, this study suggests that nmTECs play a significant role in MG pathogenesis via ectopic expression of neuromuscular molecules.

  Study JGAS000482

• Development of Novel Chondrosarcoma Organoid Models for Drug Discovery

  Chondrosarcoma is a rare and aggressive malignant bone tumor characterized by resistance to conventional chemotherapy and radiotherapy. Its pathogenesis remains poorly understood, although recurrent mutations such as IDH1 have been implicated in tumor development. We treated patients with chondrosarcoma at the Osaka International Cancer Institute and established two organoid cultures from resected tumor specimens using a modified air-liquid interface method. After serial passaging, the organoids were successfully xenografted into NOD-scid IL2Rgnull (NSG) mice. The established organoids retained key histological features and genetic characteristics of the original tumors. These organoid models provide a novel and reliable platform for studying the biology of chondrosarcoma and may facilitate the development of effective therapeutic strategies for this treatment-resistant tumor.

  Study JGAS000834

• Whole exome sequencing and RNA sequencing of cervical cancer

  We designed this study to identify molecular markers involved in the development and prognosis of cervical adenocarcinoma. In this study, we would like to elucidate the molecular biological characteristics of cervical adenocarcinoma in relation to the carcinogenesis of other cervical cancers (squamous cell carcinoma), vaginal and vulvar cancers. In addition, some squamous cell carcinomas of the cervix develop at a young age and have a poor prognosis. Furthermore, small cell carcinoma of the cervix also progresses rapidly and has a poor prognosis, making the establishment of diagnostic and therapeutic methods an urgent task.

  Study JGAS000586

• 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

• Whole-genome sequencing on hepatocellular carcinoma with nodule-in-nodule appearance reveals stepwise cancer evolution

  We examined five cases with hypovascular early HCC with hypervascular foci, so-called nodule-in-nodule HCC. Multiregional sampling was performed from both the inner hypervascular region and outer hypovascular region, together with noncancerous liver tissue and lymphocytes as controls. Comprehensive analysis of genomic aberrations, such as single nucleotide variants (SNVs) and structural variations (STVs), was performed by whole-genome sequencing.

  Study JGAS000190

• 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

• Immuno-genomic Profiling of Biopsy Specimens Predicts Neoadjuvant Chemotherapy Response in Esophageal Squamous Cell Carcinoma

  Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is primarily treated with platinum-based neoadjuvant chemotherapy (NAC). Some ESCCs respond well to NAC. However, biomarkers to predict NAC sensitivity and their response mechanism in ESCC remain unclear. We introduce a model by machine learning and validated its potential to predict the NAC response in ESCC. To create this model, we performed whole genome sequencing and RNA-seq analysis on totally 141 ESCC biopsy specimens before NAC treatment and analyzed their immuno-genomic features and association with NAC response. Neutrophils infiltration could play an important role in ESCC response to NAC. We also demonstrated that specific copy number alterations and copy number signatures in the ESCC genome were significantly associated with NAC response. The interactions between the tumor genome and immune features of ESCC are likely to be a new indicator of therapeutic capability and a new therapeutic target for ESCC, and machine learning prediction for NAC response is useful.

  Study JGAS000535

• Genetic and transcriptional landscape of plasma cells in POEMS syndrome

  POEMS syndrome is a rare paraneoplastic disease, associated with monoclonal plasma cells whose pathogenic importance remains unclear. We performed comprehensive genetic analyses of plasma cells in 20 patients with POEMS syndrome. Whole exome sequencing and targeted sequencing identified 7 recurrently mutated genes: KLHL6, LTB, EHD1, EML4, HEPHL1, HIPK1, and PCDH10. None of the driver gene mutations frequently found in multiple myeloma (MM) such as NRAS, KRAS, BRAF, and TP53 was detected. Copy number analysis showed chromosomal abnormalities shared with monoclonal gammopathy of undetermined significance (MGUS). RNA sequencing revealed a transcription profile specific to POEMS syndrome, especially in terms of tumorigenesis. Unexpectedly, disease-specific VEGFA expression was not increased in POEMS syndrome. Our study illustrates that the genetic and transcriptional profiles of plasma cells in POEMS syndrome are distinct from MM and MGUS, indicating its unique pathogenesis.

  Study JGAS000150

• Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis thymoma

  Myasthenia gravis (MG) is known to be epidemiologically associated with abnormalities of the thymus, an organ that maintains central tolerance. However, due to the complexity of the thymus, specific characteristics related to the pathogenesis of MG remain elusive. In our study, we attempted to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We found that the majority of thymomas were constituted by the cortical region, whereas the medullary region was localized in comparatively restricted areas. Moreover, the medullary region contained polygenic enrichment, MG-specific germinal center structures, and a supporting immune microenvironment. Additionally, neuromuscular medullary thymic epithelial cells (nmTECs), previously identified as MG-specific autoantigen-producing cells, were situated at the cortico-medullary junction. The immune microenvironment in the medulla was characterized by a specific chemokine pattern and specific immune cells, such as CCR7+ migratory dendritic cells (migDCs) and effector regulatory T (Treg) cells. Furthermore, similar germinal center structures and immune microenvironments were observed in the medulla during thymic hyperplasia. This study indicates that the medulla and junction areas are related to the pathology of MG, suggesting that these areas should be the focus of future studies on MG pathogenesis and drug targeting.

  Study JGAS000672

• 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

• 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 157 oral MPA-treatment samples from 66 cases (53 endometrial hyperplasia from 31 cases, 19 atypical polypoid adenomyoma from 14 cases, 1 normal endometrium from 1 case, and 84 endometrial carcinoma from 53 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 JGAS000813

• Whole genome and transcriptome sequences of hepatocellular carcinoma in patients with Fontan-associated liver disease

  Most liver cancers develop as a result of long-term liver disease caused by viruses, drugs or metabolic disorders. Fontan-associated liver disease (FALD) is a rare condition whose prevalence is increasing. We therefore conducted a multi-omics analysis targeting liver cancer arising from liver damage caused by rare diseases, with a particular focus on FALD.

  Study JGAS000904

• Whole Genome Sequencing Analysis of Adult T-cell Leukemia/Lymphoma

  In this study, we have performed the whole genome sequencing (WGS) for primary tumors from adult T-cell leukemia/lymphoma (ATL) to identify recurrent genetic mutations and structural variants.

  Study JGAS000320

• Single-cell bisulfite-seq analyses of 1-year-old prospermatogonia and adult spermatogonial stem cell

  To examine the timing of de novo methylation during human male germ cell development, single-cell bisulfite sequencing was carried out on human germ cells. FACS-purified Prospermatogonia from three teratoma patients (1-year-0-month, 1-year-5-months, and 1-year-8-months) and spermatogonial stem cells from a 29-year-old obstructive azoospermia patient with normal spermatogenesis were analyzed. The three 1-year-old prospermatogonia exhibited average methylation levels of 41.4% (23.1-54.4%, 1-year-0-month), 53.1% (32.0-62.4%, 1-year-5-months), and 32.6% (10.2-54.7%, 1-year-8-months). In contrast, adult spermatogonia showed an average level of 75.7% (73.3-76.8%). Although teratoma may have influenced the developmental timing of prospermatogonia within the same testes, prospermatogonia across all 1-year-old samples remained in an intermediate phase of DNA methylation establishment.

  Study JGAS000887

• Homozygous inactivation of CHEK2 is linked to a familial case of multiple primary lung cancer with accompanying cancers in other organs

  In clinical practice, there are a number of cancer patients with clear family histories, but not belonging to existing familial malignancies. Recent advances in genomic technologies have enhanced the possibility of identifying causative genes in such cases. Two siblings, an elder sister and a younger brother, were found to have multiple primary lung cancers at the age of 60. The former subsequently developed breast cancer, and had a history of myoma uteri. The latter had initially developed prostate cancer at the age of 59, and had a history of colon cancer. SNP genotyping revealed that approximately 10% of the genomes were homozygous in both patients. Exome sequencing revealed non-synonymous mutations in four genes in the runs of homozygosity: CHEK2, FCGRT, INPP5J, and SFI1. Evolutionary conservation of primary protein structures suggested the functional importance of the CHEK2 mutation, R474C. This mutation altered the tertiary structure of CHK2 by disrupting the salt bridge between R474 and E394. No such structural changes were observed with the other three mutated genes. Subsequent cell-based transfection analysis revealed that CHK2 R474C was unstable and scarcely activated. We concluded that CHEK2 is a causative gene in this case of familial cancer. Although homozygous inactivation of CHEK2 in mice led to cancers in multiple organs, accumulation of additional human cases is needed to establish its pathogenic role in humans.

  Study JGAS000057

• Genomic features of renal cell carcinoma developed in end-stage renal disease and dialysis

  Patients with end-stage renal disease (ESRD) or receiving dialysis have 3 ���24-fold higher risk for renal cell carcinoma (RCC). Long-term hemodialysis cause acquired cystic disease (ACD) and RCC.���But its carcinogenic mechanism and genomic features are not so clear. In this study, we analyzed whole genome and transcriptome of 38 RCCs, which were developed in ESRD patients receiving dialysis and characterized their genomic features and associations with their histology and dialysis or end-stage renal diseases.

  Study JGAS000533

• NGS-based targeted exome sequencing of osteosarcoma

  The present study aimed to identify potential genomic markers for the prediction of chemosensitivity in patients with OS using a genomic approach.

  Study JGAS000282

• Global Architecture of anti-Tumor B-Cell Immunity against Gastric Cancer

  Recent successes in tumor immunotherapies have warranted the importance of tumor immunity. Compared to the T-cell immunity, B-cell immune system in cancer is largely elusive. Here we immunogenetically profiled tumor-infiltrating B-cell and T-cell repertoires for exome- characterized diffuse-type gastric carcinoma (DGC), which is remarkable for its B-cell infiltrations, unraveling previously un-defined architectures of B-cell immunity and its interplays with T-cell immunity in cancer. We also performed transcriptome analysis to enumerate the proportions of tumor-infiltrating immune cells in the gastric cancer environment .

  Study JGAS000103

• DNA demethylation is associated with malignant progression of low-grade gliomas

  To elucidate the mechanisms of tumor progression is key to discovering strategies for treating patients with lower-grade glioma. Thus to characterize the changes in the molecular profile during malignant progression, we performed methylation array analysis (122 tumors), whole-exome sequencing (36 tumors and matched normal samples), and RNA sequencing (31 tumors). This cohort included 24 matched pairs of initial lower-grade gliomas and recurrent tumors, most of which showed malignant progression when they recurred. Nearly half of IDH-mutant glioblastomas that had progressed from lower-grade gliomas exhibited characteristic partial DNA demethylation in previously methylated genomic regions of their corresponding initial tumors, which had the glioma CpG island methylator phenotype (G-CIMP). In these glioblastomas, cell cycle-related genes were upregulated, RB and PI3K-AKT pathway genes were frequently altered. Notably, bioinformatics analysis revealed that late-replicating domain was significantly enriched in the demethylated regions that were mostly located in non-regulatory regions, suggesting that the loss of DNA methylation during malignant transformation may involve mainly passive demethylation due to a delay in maintenance of methylation during accelerated cell division. Nonetheless, a limited number of genes including IGF2BP3, which potentially drives cell proliferation, were presumed to be upregulated due to demethylation of their promoter. Thus, cell proliferation was further promoted by passive demethylation in the promoter region of these oncogenic genes. Our data indicated that demethylation of the G-CIMP profile found in a subset of recurrent gliomas reflects accelerated cell divisions accompanied by malignant transformation. Oncogenic genes activated by such epigenetic change represent potential therapeutic targets.

  Study JGAS000146

• Whole exome sequencing and RNA sequencing of cervical cancer

  We designed this study to identify molecular markers involved in the development and prognosis of cervical adenocarcinoma. In this study, we would like to elucidate the molecular biological characteristics of cervical adenocarcinoma in relation to the carcinogenesis of other cervical cancers (squamous cell carcinoma), vaginal and vulvar cancers. In addition, some squamous cell carcinomas of the cervix develop at a young age and have a poor prognosis. Furthermore, small cell carcinoma of the cervix also progresses rapidly and has a poor prognosis, making the establishment of diagnostic and therapeutic methods an urgent task.

  Study JGAS000582

• Single cell transcriptome analysis of breast invasive carcinoma

  We performed single-cell RNA-seq of breast invasive ductal carcinoma to identify the expressional heterogeneity in Luminal subtype and HER2-positive subtype.

  Study JGAS000309

• Spatial transcriptome analysis for elucidating progression of early lung adenocarcinoma

  In this study, we performed spatial transcriptome analysis of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) to identify molecular events which occur during progression of ealry lung adenocarcinoma. For the analysis, we used cancer tissues which were precisely classified by Noguchi classification. Using the obtained data, we elucidated key molecular changes during tumor cell progression and their associated microenvironment statuses.

  Study JGAS000677

• 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

• Establishment of xenogfafts and cultured cell lines from clinical samples

  The purpose of the present study was to clarify the presence or absence of alterations in the molecular properties of patient-derived xenografts (PDXs) with up to eight passages in endometrial carcinomas. Alterations in the proportion of immunohistochemically positive/negative cells for PAX8, estrogen receptor, PAX2, and PTEN were observed in established PDXs of endometrioid carcinomas and carcinosarcomas, whereas proportions of cells with AE1/AE3, TP53, ARID1A PMS2, and MSH6 were maintained. Variants of cancer-associated genes in PDX compared to those in the parental tumors were examined in two cases, a frameshift deletion in BRCA1 was observed in the parental tumor tissue, and additional genomic alterations were found in the PDXs of this case. Genomic and phenotypic alterations in endometrial carcinoma PDXs relative to the parental tumors were observed and were partly associated with endometrial cancer-specific characteristics in cellular differentiation and gene mutations.

  Study JGAS000585

• Comprehensive analyses of clinicopathological features and genomic mutations of combined hepatocellular-cholangiocarcinoma

  Combined hepatocellular and cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer. We performed whole exome sequencing to clarify the relationship between genetic mutations and clinicopathological features in cHCC-CCA.

  Study JGAS000599

• Project for Development of Innovative Research on Cancer Therapeutics;Shuttle system between petient-derived xenograft and ex vivo culture for innovative platform of evaluating drug sensitivity.

  We developed CTOS (cancer tissue-originated spheroid) panel covering diversity among patients for colorectal cancer, lung cancer and cervical small cell carcinoma. We then carried out exome sequence analysis of tumor tissues, cell lines and CTOS derived from patients to validate qualitative changes in preparation, culture, cell line, transplantation and passage of CTOS pathologically, biochemically, molecular biologically.

  Study JGAS000089

• Deciphering craniopharyngioma subtypes: Single-cell analysis of tumor microenvironment and immune networks

  Craniopharyngiomas, including both adamantinomatous (ACP) and squamous papillary (PCP) types, present significant challenges in treatment due to their proximity to critical pituitary structures. In this study, we conducted a single-cell RNA analysis to examine the tumor microenvironments (TME) of ACP and PCP. Single-cell clustering revealed a wide range of cell types, which were further categorized based on gene expression patterns. For ACP, these categories included developing epithelia, calcification, and immune response, while PCP showed developing epithelia, cell cycle, and immune response as prominent categories. Subclustering analysis unveiled different types of immune cells in both ACP and PCP TMEs, with specific patterns of immune responses. Interestingly, smaller tumors were associated with particular immune cell ratios. Furthermore, we identified specific cell-to-cell interactions within the tumor cells. In conclusion, our study has led to the development of a comprehensive cell atlas, shedding light on the molecular characteristics and intricate interplay of immune cells within the TMEs of ACP and PCP.

  Study JGAS000722

• Full length cDNA-selective sequencing of human frontal lobe

  To catalog RNA isoforms in the human brain, we applied full-length cDNA-selective sequencing (FLeCS-seq) to RNA samples extracted from the normal frontal lobe of a glioma patient. Short-read RNA-seq and long-read SMART-seq were also performed as control datasets. Additionally, we utilized ultralong-read and short-read whole-genome sequencing to phase heterozygous SNPs. By integrating these phased SNPs with FLeCS-seq reads, we identified allele-specific expressed isoforms.

  Study JGAS000877

• RNA-seq of adult T-cell leukemia-lymphoma patient-derived xenograft (PDX) models treated with the MALT1 protease inhibitor CRD-1441551

  To elucidate the therapeutic effect of MALT1 protease inhibition in adult T-cell leukemia/lymphoma (ATL), we performed RNA-seq on tumor tissues from five ATL patient-derived xenograft (PDX) models. NOG mice engrafted with each PDX model were treated with the MALT1 protease inhibitor CRD-1441551 or vehicle for 21 days, in biological triplicate (n = 3 per condition; 30 samples in total). Mouse-derived reads were removed and the remaining human reads were aligned to the human reference genome (hg19). These data underlie the gene-expression analyses reported in the associated publication.

  Study JGAS000921

• Analysis of Large Cell Neuroendocrine Carcinoma Expressing POU2F3 Using WGS

  Lung LCNEC (Large Cell Neuroendocrine Carcinoma) has a poor prognosis, and no effective treatment has yet been established. We have found that the tuft-cell marker POU2F3 is specifically expressed in some LCNEC cases. By performing Whole Genome Sequencing (WGS) on samples from 10 LCNEC patients, we aim to identify changes characteristic of LCNEC expressing POU2F3 and explore new classifications and treatment options for LCNEC.

  Study JGAS000784

• 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

• Paediatric Hepatic International Tumour Trial (JPLT2: PHITT)

  Hepatoblastoma (HBL) is the most common primary liver tumor in children. Despite their diversity in histopathological phenotype and clinical outcome, the underlying molecular aberrations have not been fully understood. Here we describe a comprehensive landscape of genomic, epigenomic, and transcriptomic heterogeneity among the 163 cases of HBLs and transitional liver cell tumors (TLCTs) collected in the multicenter clinical trial JPLT-2. The total numbers of mutational events in HBLs are very few (0.52 SNVs/Mb on exonic regions) but show a positive correlation with the age of onset. While dysregulation of Wnt-pathway related genes was observed (somatic deletion or mutations of CTNNB1 and germline or somatic mutations of APC) in 83.6% of the HBL cases, TERT promoter mutations are mainly in the elderly HBLs (> 8 years old), meeting with the proposed criteria of TLCT. These TLCT cases are clustered in the hypermethylated epigenotype in promoter and enhancer regions. Copy number analyses also revealed recurrent 11p15.5 UPD/LOHs including the IGF2/H19 region (31.6%), focal deletions in 4q35 (15.8%) and focal amplifications in 2q24.3 (7.0%) predominantly in the child and infant HBLs. Motif enrichment analysis of the specific hypomethylated enhancers in these HBL subtypes suggests specific binding of ASCL2, the regulatory transcription factor for definitive endoderm and digestive systems. Transcriptome and histochemical analysis revealed that ASCL2 is upregulated not in HCC and TLCT but in child and infant HBL, suggesting their ?cell of origin? derived from the premature hepatoblast with high proliferative potential such as intestinal epithelial cells. Systematic molecular profiling of HBL will provide a fundamental understanding of hepatoblast carcinogenesis and clues for risk stratification.

  Study JGAS000236

• Whole-exome sequencing of uterine carcinosarcoma in a young woman with HBOC (tumor-normal pair)

  This study deposits controlled-access human genomic data (tumor-normal whole-exome sequencing) from a patient with uterine carcinosarcoma and hereditary breast and ovarian cancer (HBOC) syndrome, to support reproducibility of reported genomic findings.

  Study JGAS000883

• Identification and Characterization of Cancer Mutations in Japanese LungAdenocarcinoma without Sequencing of Normal Tissue Counterparts

  We analyzed whole-exome sequencing data from 97 Japanese lung adenocarcinomapatients and identified several putative cancer-related genes and pathways. Particularly, we observed that cancer-related mutation patterns were significantly different between different ethnic groups. As previously reported, mutations in the EGFR gene were characteristic to Japanese, while those in the KRAS gene were more frequent in Caucasians. Furthermore, during the course of this analysis, we found that cancer-specific somatic mutations can be detected without sequencing normal tissue counterparts. 64% of the germline variants could be excluded using a total of 217 external Japanese exome datasets. We also show that a similar approach may beused for other three ethnic groups, although the discriminative power depends on the ethnic group. We demonstrate that the ATM gene and the PAPPA2 gene could be identified as cancer prognosis related genes. By bypassing the sequencing of normaltissue counterparts, this approach provides a useful means of not only reducing the time and cost of sequencing but also analyzing archive samples, for which normal tissue counterparts are not available.

  Study JGAS000001

• Global Architecture of anti-Tumor B-Cell Immunity against Gastric Cancer

  Recent successes in tumor immunotherapies have warranted the importance of tumor immunity. Compared to the T-cell immunity, B-cell immune system in cancer is largely elusive. Here we immunogenetically profiled tumor-infiltrating B-cell and T-cell repertoires for exome- characterized diffuse-type gastric carcinoma (DGC), which is remarkable for its B-cell infiltrations, unraveling previously un-defined architectures of B-cell immunity and its interplays with T-cell immunity in cancer. We also performed transcriptome analysis to enumerate the proportions of tumor-infiltrating immune cells in the gastric cancer environment .

  Study JGAS000141

• CAGE analysis for non-small cell lung carcinoma

  Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed. To achieve this goal, we performed CAGE (Cap Analysis of Gene Expression) to quantify promoter activities on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD). The result was followed up by by immunohistochemical analysis (IHC) in an independent group.

  Study JGAS000070

• Comprehensive molecular profiling of pulmonary pleomorphic carcinoma

  Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. Whole exome sequencing (WES) of fresh-frozen tissue samples and target-capture sequencing of formalin-fixed-paraffin-embedded (FFPE) samples were performed. Fresh-frozen tissue samples and FFPE samples were subjected to WES and target-capture sequencing as normal control, respectively. Fresh-frozen tissue samples and 56 FFPE samples were subjected to RNA-seq.

  Study JGAS000297

• 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

• Genetic drivers define transcriptomic characteristics and clonal hierarchy within intratumoral heterogeneity in adult T-cell leukemia-lymphoma

  Study JGAS000301

• Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas

  We performed RNA-sequencing in 47 patients with suspected pediatric sarcomas, to evaluate the potential utility of RNA-seq in the diagnostic process of pediatric sarcoma.

  Study JGAS000284

• The genetic analysis of circulating tumor DNA in blood of the digestive cancer patients to investigate the prognostic factors of metastasis and reccurence.

  A Darwinian evolutionary shift occurred early in the neutral evolution of advanced colorectal carcinoma (CRC) and copy number aberrations (CNA) were essential in the transition from adenoma to carcinoma. Subsequent to the primary evolution, we now focus on the evolutionary principle of the genome to foster postoperative recurrence of CRC. SO, We compared CNA, single nucleotide variance (SNV), RNA sequences between 8 primary and 11 metastatic sites from 10 CRCR cases.

  Study JGAS000221

• 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

• High Sensitivity ctDNA Analysis Using a Novel Panel and NOIR-SS Technology for Monitoring Advanced Urothelial Carcinoma

  This dataset contains sequencing data generated by targeted amplicon analysis using the NOIR-SS method in 15 patients with advanced urothelial carcinoma. Formalin-fixed paraffin-embedded (FFPE) tumor tissues (15 samples) and plasma cfDNA (50 samples) were analyzed. Tumor tissues were subjected to targeted panel sequencing to identify mutations in TP53, FGFR3, TERT, and KRAS/HRAS. Plasma cfDNA was analyzed using a tumor-informed approach focusing on the mutations identified in matched tumor tissues. Sequencing was performed on the Ion PGM or Ion S5 XL platform. Raw sequencing data are provided in FASTQ format under controlled access.

  Study JGAS000836