{"id":"hum0035","version":2,"url":"https://humandbs.dbcls.jp/research/hum0035/v2","datePublished":"2017-12-26","versions":[{"version":1,"datePublished":"2015-09-16"},{"version":2,"datePublished":"2017-12-26"},{"version":3,"datePublished":"2020-05-29"},{"version":4,"datePublished":"2020-12-14"},{"version":5,"datePublished":"2020-12-18"}],"title":{"ja":"固形腫瘍における遺伝子異常の網羅的解析","en":"Genome wide analysis of gene mutations in solid tumors"},"summary":{"aims":{"ja":"多数の固形腫瘍性疾患検体について、種々の遺伝子解析技術を用いて、固形腫瘍性疾患の発症の原因となる遺伝子異常をゲノムワイドに同定する","en":"To explore genetic alterations in solid tumors, we performed genome wide analysis using next generation sequencing methods."},"methods":{"ja":"JGAS000036： 小児横紋筋肉腫（rhabdomyosarocoma：RMS）16症例と胸膜肺芽腫（Pleuropulmonary blastoma：PPB）7症例の腫瘍組織と、対応する末梢血（非腫瘍組織）をペアでエクソーム解析を行なうことで体細胞変異を同定する。RMS 3症例、PPB 2症例については、再発時腫瘍組織も併せて解析を行う。\nJGAS000046： 神経芽腫（neuroblastoma: NB）の522症例の腫瘍組織と対応する末梢血（非腫瘍組織）および神経芽腫細胞株39検体についてSNP-chip解析とリシークエンス（NGS）による変異解析を行う。\nJGAS000088： 小児膵芽腫（pancreatoblastoma: PBL）10症例の腫瘍組織と対応する末梢血（非腫瘍組織）についてSNP-chip解析、エクソーム解析を実施。RNA-seq解析、メチル化解析については、腫瘍組織のみを対象として実施。\nJGAS000188： 小児肝芽腫（hepatoblastoma: HBL）59症例の腫瘍組織とHBL細胞株 2検体についてSNP-chip解析、Target Capture解析、RNA-seq解析、メチル化解析を実施。\nJGAS000204： 小児胚細胞腫瘍51症例の検体にSNPアレイ、全RNAシーケンス、メチル化アレイ、ターゲットキャプチャーの解析を行い、統合的なデータの解析をする。\nJGAS000246： 小児高リスク神経芽腫30症例の腫瘍組織についてRNA-seq解析、Target Capture解析を実施。","en":"JGAS000036: Whole exome sequencing (WES) for 16 rhabdomyosarocoma (RMS) and 7 pleuropulmonary blastoma (PPB) patients using tumor tissues and corresponding normal blood cells (non-tumor tissues) were performed. Relapsed tumor tissues were also analyzed in total of 5 cases.\nJGAS000046: SNP-chip analysis and targeted amplicon deep sequencing were performed using tumor tissues and corresponding normal blood cells (non-tumor tissues) from 522 neuroblastoma (NB) patients and 39 neuroblastoma cell lines.\nJGAS000088: SNP-chip and WES analyses were performed using tumor tissues and corresponding normal blood cells (non-tumor tissues) from 10 pancreatoblastoma (PBL) patients. Methylation array and RNA-seq analyses were performed using only tumor tissues.\nJGAS000188: SNP-chip, Methylation array, RNA-seq, and Target Capture Sequencing analyses were performed using tumor tissues from 59 hepatoblastoma (HBL) patients and 2 HBL cell lines.\nJGAS000204: SNP-chip, Methylation array, RNA-seq, and Target Capture Sequencing analyses were performed using tumor tissues from 51 patients with pediatric germ cell tumors.\nJGAS000246: RNA-seq and Target Capture Sequencing analyses were performed using tumor tissues from 30 high-risk neuroblastoma patients."},"targets":{"ja":"JGAS000036： RMS 16症例、PPB 7症例\nJGAS000046： NB 522症例、神経芽腫細胞株 39検体\nJGAS000088： PBL 10症例\nJGAS000188： HBL 59症例、HBL細胞株 2検体\nJGAS000204： 小児胚細胞腫瘍 51症例\nJGAS000246： 小児高リスク神経芽腫 30症例","en":"JGAS000036: 16 RMSs and 7 PPBs\nJGAS000046: 522 NBs and 39 neuroblastoma cell lines\nJGAS000088: 10 PBLs\nJGAS000188: 59 HBLs and 2 HBL cell lines\nJGAS000204: 51 patients with pediatric germ cell tumors\nJGAS000246: 30 high-risk neuroblastoma patients"},"url":{"ja":[{"url":"https://tokyoped.jp/aboutus/specialty/hemato-oncology","text":"https://tokyoped.jp/aboutus/specialty/hemato-oncology"}],"en":null}},"listingSummary":{},"releaseNote":{"ja":"このバージョンでは、神経芽腫522症例、小児膵芽腫10症例の腫瘍組織と、対応する末梢血（非腫瘍組織）、神経芽腫細胞株39検体を対象とした以下の解析結果を追加した（JGAS000046、JGAS000088）。\n・SNP-chip解析：神経芽腫522症例、小児膵芽腫10症例の腫瘍組織と、対応する末梢血（非腫瘍組織）、神経芽腫細胞株39検体\nCopy Number Variation (CNV)の決定には、GeneChip Human Mapping 250k NsplもしくはCytoscan HD（Affymetrix）を使用している。\n・NGSによるTarget amplicon deep sequencing：神経芽腫 522症例の腫瘍組織\n塩基配列型決定には、HiSeq 2000、MiSeq（Illumina）を使用している。\n・エクソーム解析：小児膵芽腫10症例の腫瘍組織と、対応する末梢血（非腫瘍組織）\nSureSelect Human ALL Exon kit（50Mb kit, v4もしくはv5）を用いてExon領域にしぼり、HiSeq 2000/2500にて平均長75-108塩基のDNA断片を解読した（Paired-end）。\n・RNA-seq解析：小児膵芽腫10症例の腫瘍組織のみ\nBioLabs NEBNext Ultra RNA Library Prep Kit for Illumina もしくはIllumina TruSeq RNA Sample Preparation Kit v2 を用いてライブラリを作製し、HiSeq 2500にて平均長108塩基断片を解読した（Paired-end）。\n・メチル化アレイ解析：小児膵芽腫10症例の腫瘍組織のみ\nInfinium MethylationEPIC（Illumina）を用いてメチル化解析を行った。","en":"Analyses data about 522 neuroblastoma (NB) patients, 39 neuroblastoma cell lines (JGAS000046), and 10 pancreatoblastoma (PBL) patients (JGAS000088) were added.\n• SNP-chip: 39 neuroblastoma cell lines and tumor tissues and peropheral blood cells (non-tumor tissues) from 522 NBs and 10 PBLs\nGeneChip Human Mapping 250k Nspl (Affymetrix) was used for genotyping.\n• Target amplicon deep sequencing: tumor tissues from 522 NBs\nHiSeq 2000, MiSeq (Illumina) was used for genotyping.\n• Exome: tumor tissues and peripheral blood cells (as non-tumor tissues) from 10 PBLs\nExons were narrowed down by using of SureSelect Human ALL Exon kit (50Mb kit, v4/v5) and read by Illumina HiSeq 2000/2500 (paired-end: 75-108 bp).\n• RNA-seq: tumor tissues from 10 PBLs\nRNA library was builded using BioLabs NEBNext Ultra RNA Library Prep Kit for Illumina or Illumina TruSeq RNA Sample Preparation Kit v2, and read by Illumina HiSeq 2500 (paired-end: 108 bp).\n• Methylation array: tumor tissues from 10 PBLs\nInfinium MethylationEPIC (Illumina) was used for methylation analysis."},"dataProviders":[{"name":{"ja":"滝田 順子","en":"Junko Takita"},"organization":{"name":{"ja":"東京大学大学院医学系研究科 生殖・発達・加齢医学専攻 小児医学講座","en":"Graduate School of Medicine, The University of Tokyo"}}}],"researchProjects":[{"name":{"ja":"東京大学小児科血液腫瘍グループ/次世代がん研究シーズ戦略的育成プログラム「統合的ゲノムスキャニングによる難治性小児固形腫瘍の新規標的分子の探索」","en":"Department of Pediatrics, Hematology/Oncology Group"},"url":{"ja":null,"en":null}},{"name":{"ja":"次世代がん研究シーズ戦略的育成プログラム -統合的ゲノムスキャニングによる難治性小児固形腫瘍の新規標的分子の探索-","en":"Project for Development of Innovative Research on Cancer Therapeutics -Investigation of novel molecular targets of intractable pediatric solid tumors using integrated genetic analysis-"},"url":{"ja":null,"en":null}}],"grants":[{"title":{"ja":"統合的ゲノムスキャニングによる難治性小児固形腫瘍の新規標的分子の探索","en":"Investigation of novel molecular targets of intractable pediatric solid tumors using integrated genetic analysis"},"agency":{"ja":"日本医療研究開発機構（AMED） 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), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP15cm0106065"]},{"title":{"ja":"小児固形腫瘍の転移・再発を制御するクローン進化の時空的かつ網羅的ゲノム解析研究","en":"Studies on clonal evolutions which regulate metastasis and relapse in pediatric solid tumors using spatiotemporal and comprehensive genome-wide analysis"},"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":["26293242"]},{"title":{"ja":"小児胚細胞腫瘍の包括的なゲノム解析及び治療標的の探索","en":"Comprehensive genetic analysis and searching for drug target discovery in pediatric germ cell tumors"},"agency":{"ja":"2019年度公益財団法人がんの子どもを守る会治療研究助成金","en":"Children's Cancer Association of Japan: Therapeutic Research Grants"},"grantIds":null}],"relatedPublications":[{"title":"Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.","doi":"https://doi.org/10.1038/ncomms8557","datasets":["JGAD000036"]},{"title":"Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma.","doi":"https://doi.org/10.1158/0008-5472.can-13-2470","datasets":["JGAD000036"]},{"title":"Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis.","doi":"https://doi.org/10.18632/oncotarget.22495","datasets":["JGAD000046"]},{"title":"Integrated molecular characterization of the lethal pediatric cancer pancreatoblastoma.","doi":"https://doi.org/10.1158/0008-5472.CAN-17-2581","datasets":["JGAD000088"]},{"title":"Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets","doi":"https://doi.org/10.1038/s41698-020-0125-y","datasets":["JGAD000270"]},{"title":"Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets","doi":"https://doi.org/10.1038/s42003-020-01267-8","datasets":["JGAD000289"]}],"datasets":["JGAD000036","JGAD000088","JGAD000046"],"controlledAccessUsers":[{"principalInvestigator":{"en":"Jiguang Wang"},"affiliation":{"en":"WangLab, The Hong Kong university of science and technology"},"country":{"ja":"中国","en":"China"},"researchTitle":{"en":"Germline and somatic mutations in pediatric germ cell tumor."},"periodStart":"2022-06-03","periodEnd":"2024-04-03","datasets":["JGAD000289"]},{"principalInvestigator":{"en":"Weng Chuan Peng"},"affiliation":{"en":"Research, Princess Maxima Center for Pediatric Oncology"},"country":{"ja":"オランダ","en":"Netherlands"},"researchTitle":{"en":"Towards understanding pediatric liver tumors"},"periodStart":"2023-08-21","periodEnd":"2027-06-01","datasets":["JGAD000270"]},{"principalInvestigator":{"ja":"浜田 道昭","en":"Michiaki Hamada"},"affiliation":{"ja":"浜田研究室, 理工学術院, 早稲田大学","en":"Hamada Laboratory, Faculty of Science and Engineering, Waseda University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"RNA標的創薬データベースの構築","en":"Construction of RNA-targeted Drug Discovery Database"},"periodStart":"2023-01-05","periodEnd":"2027-10-31","datasets":["JGAD000036","JGAD000046","JGAD000088","JGAD000270","JGAD000289","JGAD000346"]},{"principalInvestigator":{"en":"Yujie Tang"},"affiliation":{"en":"Department of Histoembryology, Genetics and Developmental Biology, College of Basic Medical Sciences, Shanghai Jiao Tong University"},"country":{"ja":"中国","en":"China"},"researchTitle":{"en":"The key molecular mechanisms underlying the oncogenesis and progression of neuroblastoma and hepatoblastoma"},"periodStart":"2023-03-08","periodEnd":"2027-12-31","datasets":["JGAD000270"]},{"principalInvestigator":{"en":"leendert looijenga"},"affiliation":{"en":"Research and Development, Looijenga Group, Prinses Maxima Centrum"},"country":{"ja":"オランダ","en":"Netherlands"},"researchTitle":{"en":" Histological and molecular characterization of extracranial germ cell tumors: towards an optimal patient risk stratification."},"periodStart":"2025-04-28","periodEnd":"2027-03-31","datasets":["JGAD000289"]},{"principalInvestigator":{"en":"Ching Lau"},"affiliation":{"en":"Pediatric Oncology, The Jackson Lab for Genomic Medicine"},"country":{"ja":"アメリカ合衆国 (コネチカット州)","en":"Connecticut, United States"},"researchTitle":{"en":"Development of new DNA methylation-based classifier for brain tumors"},"periodStart":"2026-04-06","periodEnd":"2027-01-16","datasets":["JGAD000289"]}]}