{"id":"hum0030","version":5,"url":"https://humandbs.dbcls.jp/research/hum0030/v5","datePublished":"2026-04-22","versions":[{"version":1,"datePublished":"2015-04-21"},{"version":2,"datePublished":"2024-05-10"},{"version":3,"datePublished":"2024-07-05"},{"version":4,"datePublished":"2025-07-01"},{"version":5,"datePublished":"2026-04-22"}],"title":{"ja":"婦人科臓器に発生する悪性腫瘍の発症に関連する分子生物学的異常の検索","en":"The Molecular Biological Analysis about Occurrence and Malignant Transformation in gynecological carcinogenesis"},"summary":{"aims":{"ja":"卵巣明細胞腺がんと他の組織型の卵巣がんにおけるゲノムコピー数の違いを比較することに加え、全エクソンシークエンス、RNAシークエンスにより、卵巣明細胞腺がんの分子生物学的特徴を明らかにする。さらに、高異型度卵巣漿液性がんにおいても同様の網羅的ゲノム解析を行い、相同組換修復欠損のバイオマーカー、サブタイプ、予後規定因子を同定し、PARP阻害薬の有用性についても検討する。さらに、全エクソンシークエンス解析結果をもとに相同組換え修復欠損（HRD）の有無を判定し、HRD陽性症例に対するPARP阻害薬オラパリブの有効性・安全性を調べる医師主導治験を行う。\nまた、子宮体がんにおける免疫制御メカニズムを理解することは、免疫療法戦略の改善に重要である。そのため、腫瘍免疫微小環境とHLAクラスI発現の関係を解明することで、特にCD8+ T細胞浸潤パターンへの影響を明らかにする。異なる組織学的、分子生物学的サブタイプにおける免疫回避の分子基盤を解明することで、個別化免疫療法の開発に貢献することを目指す。","en":"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.\nUnderstanding 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":{"ja":"がんゲノムコピー数解析（ゲノムワイドSNPタイピングアレイを使用し約26万個のSNPプローブの蛍光強度を測定し、がんと正常を比較することでコピー数異常を検出する）、Whole Exome sequencing、RNA-seq、メチル化アレイ、発現アレイ、Target bisulfite sequencing","en":"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.\nWhole Exome sequencing and RNA-seq\nMethylation array and Expression array\nTarget bisulfite sequencing"},"targets":{"ja":"卵巣がん57（類内膜がん12）＋111＋31＋189症例、子宮体がん86症例","en":"Ovarian cancer: 57 cases (12 endometrioid carcinoma) + 111 cases + 31 + 189 cases, Endometrial cancer: 86 cases"},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"ゲノムワイド\nCNV\n配列決定\n発現\nメチル化","en":"Genome-wide CNV analysis, sequencing, expression profiling, methylation profiling"},"targets":{"ja":"卵巣癌：57＋111＋31＋189症例\n子宮体癌：86症例\n（日本人）","en":"57 + 111 + 31 + 189 Ovarian carcinomas\n86 Endometrial cancers\n(Japanese)"},"typeOfData":{"ja":"SNP-chip\nNGS\n（Exome、RNA-seq、Target bisulfite-seq）\nメチル化アレイ\nヒト全ゲノム発現アレイ","en":"SNP-chip, NGS (Exome, RNA-seq, Target bisulfite-seq), Methylation array, Expression array"}},"releaseNote":{"ja":"子宮体がん86症例の腫瘍組織から抽出したDNAを用いたHLA-A領域のTarget bisulfite sequencing解析データをfastqファイル形式で提供する。","en":"DNAs extracted from tumor tissues of 86 endometrial cancer patients were used for the HLA-A region targeted bisulfite sequencing analysis. Fastq files are provided."},"dataProviders":[{"name":{"ja":"織田 克利","en":"Katsutoshi Oda"},"organization":{"name":{"ja":"東京大学医学部 産科婦人科学教室","en":"Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo"}}}],"researchProjects":[],"grants":[{"title":{"ja":"統合的ゲノム解析によるがん細胞集団進化の解明","en":"An Integrated Genomic Analysis on Evolution of Cancer Cell Population"},"agency":{"ja":"科学研究費助成事業 基盤研究（S）","en":"KAKENHI Grant-in-Aid for Scientific Research (S)"},"grantIds":["24221011"]},{"title":{"ja":"子宮体癌・卵巣癌においてアポトーシスを誘導する新規分子標的治療法の探","en":"Search for the New Molecular Targeted Therapies and Biomarkers Inducing Apoptosis in Endometrial Carcinoma and Ovarian Carcinoma"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["26462515"]},{"title":{"ja":"卵巣明細胞腺癌における遺伝子プロファイルに基づく新規分子標的治療法の探索","en":"Search for the New Molecular Targeted Therapies Based on Genetic Profiles of Ovarian Clear Cell Carcinoma"},"agency":{"ja":"科学研究費助成事業 若手研究（B）","en":"KAKENHI Grant-in-Aid for Young Scientists (B)"},"grantIds":["25861473"]},{"title":{"ja":"「分子プロファイリングによる新規標的同定を通じた難治がん治療法開発」 （進行性卵巣がんの治療感受性を規定する遺伝子変異の同定）","en":"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)"},"agency":{"ja":"次世代がん研究シーズ戦略的育成プログラム（P-DIRECT）","en":"Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT)"},"grantIds":["11114014"]},{"title":{"ja":"卵巣明細胞癌におけるSWI/SNFクロマチンリモデリング複合体の異常と発癌過程","en":"Carcinogenesis and Disorder of SWI/SNF Chromatin Remodeling Complex in Ovarian Clear Cell Carcinoma"},"agency":{"ja":"科学研究費助成事業 若手研究（B）","en":"KAKENHI Grant-in-Aid for Young Scientists (B)"},"grantIds":["22K16873"]},{"title":{"ja":"卵巣癌における相同組換修復欠損に着目した新規分子標的治療法の探索","en":"Investigation of Novel Molecularly Targeted Therapies Focusing on Homologous Recombination Repair Defeciency in Ovarian Cancer"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["18K09249"]},{"title":{"ja":"卵巣癌におけるゲノム解析とオルガノイドによる薬剤感受性試験の臨床的有用性の検証","en":"Clinical utility of genetic analysis and organoid-based drug sensitivity testing in ovarian cancer."},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["21H03074"]},{"title":{"ja":"卵巣癌/子宮体癌における薬剤感受性メチル化診断キットの開発とLiquid Biopsyへの応用","en":"Development of a Drug-Sensitive Methylation Diagnostic Kit and Application to Liquid Biopsy for Ovarian/Uterine Cancer"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["24K02584"]}],"relatedPublications":[{"title":"Integrated Copy Number and Expression Analysis Identifies Profiles of Whole-Arm Chromosomal Alterations and Subgroups with Favorable Outcome in Ovarian Clear Cell Carcinomas","doi":"https://doi.org/10.1371/journal.pone.0128066","datasets":["JGAD000022","JGAD000682"]},{"title":"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":"https://doi.org/10.1080/2162402x.2017.1338996","datasets":["JGAD000682"]},{"title":"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":"https://doi.org/10.1136/jitc-2019-000375","datasets":["JGAD000682"]},{"title":"Integrated genomic/epigenomic analysis stratifies subtypes of clear cell ovarian carcinoma, highlighting their cellular origin","doi":"https://doi.org/10.1038/s41598-024-69796-4","datasets":["JGAD000682"]},{"title":"HLA class I dysregulation and immune microenvironment across endometrial cancer molecular subtypes","doi":null,"datasets":["JGAD001041"]}],"datasets":["JGAD000022","JGAD000682","JGAD000931","JGAD001041"],"controlledAccessUsers":[{"principalInvestigator":{"ja":"小西 郁生","en":"Ikuo Konishi"},"affiliation":{"ja":"婦人科産科学, 京都大学大学院医学研究科器官外科学","en":"Department of Gynecology and Obstetrics, Kyoto University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"多様な臨床情報を考慮した婦人科悪性腫瘍患者のオミックス解析（全ゲノム・全トランスクリプトーム・プロテオーム・メタボローム解析）による個別化治療の探索","en":"Integrated analyses of omics (genomics, transcriptomics, proteomics and metabolomics) associated with clinical variables for developing indivisualized treatment in gynecologycal malignancy"},"periodStart":"2015-07-03","periodEnd":"2017-09-04","datasets":["JGAD000022"]},{"principalInvestigator":{"ja":"万代 昌紀","en":"Masaki Mandai"},"affiliation":{"ja":"婦人科学産科学教室, 京都大学医学部医学研究科","en":"department of Gynecology and Obstetrics, Kyoto University Faculty of Medicene"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"多様な臨床情報を考慮した婦人科悪性腫瘍患者のオミックス解析（全ゲノム・全トランスクリプトーム・プロテオーム・メタボローム解析）による個別化治療の探索","en":"Integrated analyses of omics (genomics, transcriptomics, proteomics and metabolomics) associated with clinical variables for developing indivisualizedtreatment in gynecological malignancy"},"periodStart":"2018-10-04","periodEnd":"2025-04-14","datasets":["JGAD000022"]},{"principalInvestigator":{"ja":"松村 謙臣","en":"Noriomi Matsumura"},"affiliation":{"ja":"産科婦人科学教室, 近畿大学医学部","en":"Obstetrics and Gynecology, Kindai University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"JGOG3017-TR1：エクソームシークエンスデータを有する卵巣明細胞癌のRNAseq解析","en":"Integrated multi-omics analysis for ovarian clear cell adenocarcinoma: JGOG3017-TR1"},"periodStart":"2024-10-15","periodEnd":"2027-12-31","datasets":["JGAD000022","JGAD000682","JGAD000931"]},{"principalInvestigator":{"ja":"山口 建","en":"Ken Yamaguchi"},"affiliation":{"ja":"婦人科学産婦人科学教室, 京都大学","en":"Gynecology and Obstetrics, Kyoto University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"JGOG3017-TR1：エクソームシークエンスデータを有する卵巣明細胞癌のRNAseq解析","en":"Integrated multi-omics analysis for ovarian clear cell adenocarcinoma: JGOG3017-TR1"},"periodStart":"2024-10-22","periodEnd":"2027-12-31","datasets":["JGAD000022","JGAD000682","JGAD000931"]}]}