NBDC Research ID: hum0030.v4

 

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.

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

Participants/Materials: Ovarian cancer: 57 cases (12 endometrioid carcinoma) + 111 cases + 31 + 189 cases

 

Dataset IDType of DataCriteriaRelease 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

*Release Note

* Data users need to apply an application for Using NBDC Human Data to reach the Controlled-access Data. Learn more

 

MOLECULAR DATA

JGAS000022

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

 

Exome (JGAS000560)

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

 

RNA-seq

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

 

Methylation array

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

 

Expression array

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

 

Exome (JGAS000789)

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

 

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):

NameTitleProject 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

TitleDOIDataset 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

 

USERS (Controlled-access Data)

Principal InvestigatorAffiliationCountry/RegionResearch TitleData 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 2024/10/15-2025/12/31
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 2024/10/22-2025/12/31