NBDC Research ID: hum0030.v5
SUMMARY
Aims: To clarify the biological difference between clear cell carcinoma and other histological subtypes in ovarian carcinomas by comparing copy number variants, and to identify molecular subtypes and carcinogenesis in clear cell ovarian carcinomas by whole-exome sequencing and RNA-sequencing. Then, characterize high-grade serous carcinomas by NGS-based, integrative genomic analyses, with focus on homologous recombination deficiency, molecular subtypes, and prognostic factors and effectiveness of PARP inhibitor. Based on the results of whole-exome sequencing, an investigator-initiated, phase 2 clinical trial will be conducted to evaluate the efficacy and safety of the PARP inhibitor olaparib in HRD-positive cases.
Understanding the immune regulatory mechanisms in endometrial cancer is crucial for improving immunotherapy strategies. To elucidate the relationship between the tumor immune microenvironment and HLA class I expression, with a particular focus on their impact on CD8+ T cell infiltration patterns. By investigating the molecular basis of immune evasion across different histological and molecular subtypes, we will generate evidence that will contribute to the development of personalized immunotherapy strategies.
Methods:
Copy Number Variation Analysis: Gene Chip Human Mapping 250K Nsp Arrays were used for detecting the signal intensity of about 260 thousands SNPs and intensities of ovarian clear cell carcinoma were compared to the ones of non-carcinoma.
Whole Exome sequencing and RNA-seq
Methylation array and Expression array
Target bisulfite sequencing
Participants/Materials: Ovarian cancer: 57 cases (12 endometrioid carcinoma) + 111 cases + 31 + 189 cases, Endometrial cancer: 86 cases
| Dataset ID | Type of Data | Criteria | Release Date |
|---|---|---|---|
| JGAS000022 | Copy Number Variations in cancer genome | Controlled-access (Type I) | 2015/04/21 |
| JGAS000560 | NGS (Exome, RNA-seq) | Controlled-access (Type I) | 2024/05/10 |
| JGAS000560 (Data addition) | Methylation array, Expression array | Controlled-access (Type I) | 2024/07/05 |
| JGAS000789 | NGS (Exome) | Controlled-access (Type I) | 2025/07/01 |
| JGAS000897 | NGS (Target bisulfite-seq) | Controlled-access (Type I) | 2026/04/22 |
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MOLECULAR DATA
| Participants/Materials: |
Surgical samples were obtained from 57 patients (31 clear cell carcinomas, 14 serous adenocarcinomas, and 12 endometrioid adenocarcinomas) |
| Targets | genome wide CNVs |
| Target Loci for Capture Methods |
- |
| Platform | Affymetrix [GeneChip Human Mapping 250K Nsp Array] |
| Source | gDNAs extracted from ovarian cancer cells and peripheral blood cells |
| Cell Lines | - |
| Library Construction (kit name) | GeneChip Human Mapping 250K Nsp Array |
| Algorithm for detecting CNVs (software) | genome imbalance map (GIM) algorithm (doi:10.1016/j.bbrc.2005.06.040) |
| CNV number | 262,264 CNVs |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000022 |
| Total Data Volume | 17.5 GB |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
High-grade serous ovarian carcinoma (ICD10: C56.12): 78 cases (tumor tissue: 82 samples, non-tumor tissue: 78 samples) Ovarian clear cell adenocarcinoma (ICD10: C56.14): 78 cases (tumor tissue: 78 samples, non-tumor tissue: 78 samples) |
| Targets | Exome |
| Target Loci for Capture Methods | - |
| Platform | Illumina [HiSeq 2000] |
| Library Source | DNAs extracted from tumor tissues and non-tumor tissues (peripheral blood cells) |
| Cell Lines | - |
| Library Construction (kit name) | SureSelect Human All Exon kit v4, SureSelect Human All Exon kit v5 |
| Fragmentation Methods | Ultrasonic fragmentation (Covaris) |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 100 bp x 2 |
| Mapping Methods | BWA, Novoalign |
| Mapping Quality | MAPQ>20 |
| Reference Genome Sequence | hg19 |
| Coverage (Depth) | tumor 115.6, normal 108.4 |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000682 |
| Total Data Volume | 5.6 TB (fastq, bam) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
High-grade serous ovarian carcinoma (ICD10: C56.12): 77 cases (tumor tissue: 77 samples) |
| Targets | RNA-seq |
| Target Loci for Capture Methods | - |
| Platform | Illumina [HiSeq 2000] |
| Library Source | RNAs extracted from tumor tissues |
| Cell Lines | - |
| Library Construction (kit name) | TruSeq Stranded mRNA LT Sample Prep Kit |
| Fragmentation Methods | Including library prep kit protocol |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 100 bp x 2 |
| Mapping Methods | STAR (V.2.5.2a) |
| Mapping Quality | MAPQ>20 |
| Reference Genome Sequence | hg19 |
| Detecting method for read count (software) | Cufflinks (v2.1.1) |
| QC Methods | - |
| Gene Number | 38,515 genes |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000682 |
| Total Data Volume | 5.6 TB (fastq, bam, csv [FPKM]) |
| Comments (Policies) | NBDC policy |
| Participants/Materials: |
High-grade serous ovarian carcinoma (ICD10: C56.12): 97 cases (tumor tissue: 92 samples, non-tumor tissue: 5 samples) Ovarian clear cell adenocarcinoma (ICD10: C56.14): 85 cases (tumor tissue: 82 samples, non-tumor tissue: 3 samples) |
| Targets | Methylation array |
| Target Loci for Capture Methods |
- |
| Platform | Illumina [Infinium HumanMethylation450 BeadChip] |
| Source | DNAs extracted from tumor tissues and non-tumor tissues (peripheral blood cells) |
| Cell Lines | - |
| Library Construction (kit name) | Infinium HumanMethylation450 BeadChip |
| Algorithms for Calculating Methylation-rate (software) | Genome Studio |
| Filtering Methods | - |
| Normalization of methylation array | Following the standard protocol of Genome Studio |
| Probe Number | 485577 |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000682 |
| Total Data Volume | 2.9 GB (txt) |
| Comments (Policies) | NBDC policy |
| Participants/Materials: |
Ovarian clear cell adenocarcinoma (ICD10: C56.14): 89 cases (tumor tissue: 89 samples) |
| Targets | Expression array |
| Target Loci for Capture Methods |
- |
| Platform | Affymetrix [GeneChip® Human Genome U133 Plus 2.0 Array] |
| Source | RNAs extracted from tumor tissues |
| Cell Lines | - |
| Library Construction (kit name) | GeneChip® 3’ IVT Express Kit |
| Filtering Methods | - |
| Analysis Software | GeneChip® Operating Software (GCOS, Affymetrix) |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000682 |
| Total Data Volume | 2.9 GB (CEL) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
Ovarian cancer (ICD10: C56, D391): 189 cases (tumor tissue: 190, non-tumor tissue: 189) Ovarian High-Grade Serous Carcinoma: 161 cases (tumor tissue: 162, non-tumor tissue 161) Ovarian Endometrioid Carcinoma: 5 cases (tumor tissue: 5, non-tumor tissue 5) Ovarian Carcinosarcoma: 2 cases (tumor tissue: 2, non-tumor tissue 2) Ovarian De-differentiated Carcinoma: 2 cases (tumor tissue: 2, non-tumor tissue 2) Ovarian Clear Cell Carcinoma: 10 cases (tumor tissue: 10, non-tumor tissue 10) Ovarian Metastatic Tumors: 4 cases (tumor tissue: 4, non-tumor tissue 4) Ovarian Borderline Tumors: 2 cases (tumor tissue: 2, non-tumor tissue 2) Ovarian Mucinous Carcinoma/Borderline: 3 cases (tumor tissue: 3, non-tumor tissue 3) Ovarian Low-Grade Serous Carcinoma: 1 case (tumor tissue: 1, non-tumor tissue 1) |
| Targets | Exome |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NextSeq 500] |
| Library Source | DNAs extracted from tumor tissues and non-tumor tissues (peripheral blood cells) |
| Cell Lines | - |
| Library Construction (kit name) | Custom-made probes were designed to hybridize and capture the genomic DNA of the target genes of 4327 single nucleotide polymorphisms within the targeted gene regions. |
| Fragmentation Methods | - |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 150 bp x 2 |
| Mapping Methods | BWA, Novoalign |
| Mapping Quality | MAPQ>20 |
| Reference Genome Sequence | hg38 |
| Coverage (Depth) | tumor 152.0, normal 81.5 |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000931 |
| Total Data Volume | 6.4 TB (fastq, bam) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
Endometrial cancer (ICD10: C549): 86 cases tumor tissue (frozen uterine corpus): 86 samples |
| Targets | Target bisulfite sequencing |
| Target Loci for Capture Methods | HLA-A (chr6:29,943,268-29,943,632) |
| Platform | Illumina [MiSeq] |
| Library Source | DNAs extracted from tumor tissues |
| Cell Lines | - |
| Library Construction (kit name) | NEBNext Ultra II DNA Library Prep Kit for Illumina |
| Fragmentation Methods | PCR |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 251 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD001041 |
| Total Data Volume | 1.7 GB (fastq) |
| Comments (Policies) | NBDC policy |
DATA PROVIDER
Principal Investigator: Katsutoshi Oda
Affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo
Project / Group Name: -
Funds / Grants (Research Project Number):
| Name | Title | Project Number |
|---|---|---|
|
KAKENHI Grant-in-Aid for Scientific Research (S) |
An Integrated Genomic Analysis on Evolution of Cancer Cell Population |
24221011 |
|
KAKENHI Grant-in-Aid for Scientific Research (C) |
Search for the New Molecular Targeted Therapies and Biomarkers Inducing Apoptosis in Endometrial Carcinoma and Ovarian Carcinoma |
26462515 |
|
KAKENHI Grant-in-Aid for Young Scientists (B) |
Search for the New Molecular Targeted Therapies Based on Genetic Profiles of Ovarian Clear Cell Carcinoma |
25861473 |
|
Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) |
Development of the Intractable Cancer Therapies through the New Target Identification by the Molecular Profiling (The Identification of the Gene Variation to Regulate the Treatment Sensitivity of the Progressive Ovarian Cancer) |
11114014 |
| KAKENHI Grant-in-Aid for Young Scientists (B) | Carcinogenesis and Disorder of SWI/SNF Chromatin Remodeling Complex in Ovarian Clear Cell Carcinoma | 22K16873 |
| KAKENHI Grant-in-Aid for Scientific Research (C) | Investigation of Novel Molecularly Targeted Therapies Focusing on Homologous Recombination Repair Defeciency in Ovarian Cancer | 18K09249 |
| KAKENHI Grant-in-Aid for Scientific Research (B) | Clinical utility of genetic analysis and organoid-based drug sensitivity testing in ovarian cancer. | 21H03074 |
| KAKENHI Grant-in-Aid for Scientific Research (B) | Development of a Drug-Sensitive Methylation Diagnostic Kit and Application to Liquid Biopsy for Ovarian/Uterine Cancer | 24K02584 |
PUBLICATIONS
| Title | DOI | Dataset ID | |
|---|---|---|---|
| 1 | Integrated Copy Number and Expression Analysis Identifies Profiles of Whole-Arm Chromosomal Alterations and Subgroups with Favorable Outcome in Ovarian Clear Cell Carcinomas | doi: 10.1371/journal.pone.0128066 | JGAD000022 JGAD000682 |
| 2 | The frequency of neoantigens per somatic mutation rather than overall mutational load or number of predicted neoantigens per se is a prognostic factor in ovarian clear cell carcinoma | doi: 10.1080/2162402X.2017.1338996 | JGAD000682 |
| 3 | Neoantigen load and HLA-class I expression identify a subgroup of tumors with a T-cell-inflamed phenotype and favorable prognosis in homologous recombination-proficient high-grade serous ovarian carcinoma | doi: 10.1136/jitc-2019-000375 | JGAD000682 |
| 4 | Integrated genomic/epigenomic analysis stratifies subtypes of clear cell ovarian carcinoma, highlighting their cellular origin | doi: 10.1038/s41598-024-69796-4 | JGAD000682 |
| 5 | HLA class I dysregulation and immune microenvironment across endometrial cancer molecular subtypes | JGAD001041 |
USERS (Controlled-access Data)
| Principal Investigator | Affiliation | Country/Region | Research Title | Data in Use (Dataset ID) | Period of Data Use |
|---|---|---|---|---|---|
| Ikuo Konishi | Kyoto University | JGAD000022 | 2015/07/13-2017/03/31 | ||
| Masaki Mandai | Kyoto University Faculty of Medicene, department of Gynecology and Obstetrics | Integrated analyses of omics (genomics, transcriptomics, proteomics and metabolomics) associated with clinical variables for developing indivisualizedtreatment in gynecological malignancy | JGAD000022 | 2018/10/04-2025/03/31 | |
| Noriomi Matsumura | Department of Obstetrics and Gynecology, Faculty of Medicine, Kindai University | Japan | Integrated multi-omics analysis for ovarian clear cell adenocarcinoma: JGOG3017-TR1 | JGAD000022, JGAD000682 | 2024/10/15-2027/12/31 |
| Ken Yamaguchi | Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine, Kyoto University | Japan | Integrated multi-omics analysis for ovarian clear cell adenocarcinoma: JGOG3017-TR1 | JGAD000022, JGAD000682 | 2024/10/22-2027/12/31 |
| Ryusuke Murakami | Gynecology and Obstetrics, Graduate School of Medicine and Faculty of Medicine, Kyoto University | Japan | Integrated multi-omics analysis for ovarian clear cell adenocarcinoma: JGOG3017-TR1 | JGAD000931 | 2025/09/26-2027/12/31 |
| Noriomi Matsumura | Department of Obstetrics and Gynecology, Faculty of Medicine, Kindai University | Japan | Integrated multi-omics analysis for ovarian clear cell adenocarcinoma: JGOG3017-TR1 | JGAD000931 | 2025/09/29-2027/12/31 |
