{"id":"hum0006","version":1,"url":"https://humandbs.dbcls.jp/research/hum0006/v1","datePublished":"2014-01-31","versions":[{"version":1,"datePublished":"2014-01-31"},{"version":2,"datePublished":"2017-06-05"},{"version":3,"datePublished":"2017-09-01"},{"version":4,"datePublished":"2019-02-13"},{"version":5,"datePublished":"2022-08-08"},{"version":6,"datePublished":"2026-06-03"}],"title":{"ja":"脳腫瘍のゲノム・遺伝子解析とその臨床病理学的意義の解明","en":"Genomic and Genetic Analysis of Brain Tumors and Analysis of Their Clinicopathological Significance"},"summary":{"aims":{"ja":"脳腫瘍は予後不良の疾患であり、手術、放射線治療、化学療法などの集学的治療を行っても再発することが多い。そのため、脳腫瘍の発症や悪性化に関与する遺伝子異常を同定し、その臨床病理学的意義を解明することは重要な課題である。本研究では、脳腫瘍および非腫瘍組織を対象として遺伝子異常を包括的に解析し、腫瘍の悪性度、予後、および治療反応性との関連を検討する。また、画像情報を含む臨床病理学的情報と分子情報を統合し、バイオインフォマティクスおよび人工知能技術を活用した解析を行うことで、新たな診断法、予後予測法、およびバイオマーカーの開発を目指す。","en":"The identification of genomic/genetic alterations in brain tumors (gliomas) and analysis of their clinicopathological significance.\nBrain tumors are diseases with a very poor prognosis and recurrence is almost inevitable even with multidisciplinary treatment. Therefore, it is important to elucidate genetic aberrations associated with the development or malignant transformation of brain tumors. In this study, we will comprehensively analyze molecular landscapes in brain tumors. We will also investigate how these are involved in the response to various therapies to establish new molecular therapies for brain tumors. In addition, we will develop new diagnostic methods and biomarkers by comparing clinicopathological information with molecular profiles and analyze the relationship between diagnosis, prognosis prediction, and therapeutic response prediction using bioinformatics and artificial intelligence."},"methods":{"ja":"Illumina HiSeq 2000を使用したExome解析、RNA-seq解析、および、メチレーションアレイ解析\nIllumina HiSeq 2500を使用した血管奇形組織由来DNAを用いたターゲットシーケンス解析\nNanopore PromethIONを使用した左前頭葉正常部位由来DNA/RNAを用いたFLeCS-seq、SMART-seq、ultralong-read WGS解析、Element AVITIを使用したRNA-seq解析、Illumina NovaSeq 6000を使用したshort-read WGS解析","en":"Exome sequencing, RNA sequencing and Methylation array were performed. Matched normal DNA was also used for Exome sequencing.\nTargeted DNA sequencing for vascular malformation samples was conducted to investigate somatic mutations.\nFLeCS-seq, SMART-seq, RNA-seq, short-read WGS, and ultralong-read WGS analyses for normal left frontal lobe tissues were performed."},"targets":{"ja":"アストロサイトーマ6症例の初発時の腫瘍組織、再発時の腫瘍組織、および、末梢血（非腫瘍組織）\nオリゴデンドログリオーマ12症例の初発時の腫瘍組織、再発時の腫瘍組織、および、末梢血（非腫瘍組織）\nオリゴデンドログリオーマ4症例の初発時の2カ所の別の部位の腫瘍組織、および、末梢血（非腫瘍組織）\nグリオーマ（小脳17症例、視床14症例、大脳8症例）の腫瘍組織、および、末梢血（非腫瘍組織）\nグリオーマ94症例の腫瘍組織（初発時、再発時ペアを含む114検体）、および末梢血（非腫瘍組織）\n脳海綿状血管奇形12症例、椎体血管腫1症例、眼窩内海綿状血管奇形3症例の病変組織および末梢血\nグリオーマ1症例の左前頭葉の正常部位","en":"Surgical specimen obtained from 6 patients with astrocytoma (primary and matched recurrent samples) and paired normal peripheral blood cells (total: 23 samples).\nSurgical specimen obtained from 16 patients with oligodendroglioma (12 primary and matched recurrent samples, 8 samples obtained from 4 patients by multi-sampling)\nSurgical specimen obtained from patients with gliomas (17 patients with diffuse cerebellar glioma, 8 patients with cerebral glioblastoma and 14 patients with thalamic glioma)\nSurgical specimen obtained from 94 patients with gliomas, including primary and matched recurrent samples (total 114 samples) and paired normal blood cells\nTwelve cerebral cavernous malformations, 1 vertebral hemangioma, 3 orbital cavernous malformations, and respective paired peripheral blood samples\nNormal left frontal lobe tissues from a patient with glioma"},"url":{"ja":null,"en":null}},"listingSummary":{},"releaseNote":{"ja":"このバージョンでは、アストロサイトーマ6症例の初発時・再発時の腫瘍組織および末梢血（非腫瘍組織）から抽出したDNAを用いたExome解析の結果をbamファイルにて提供する。SureSelect Human All Exon v.4を用いてExon領域にしぼり、Illumina 社 HiSeq 2000にて平均長100塩基を解読した（Paired-end）。","en":"DNAs extracted from brain tumors (6 astrocytomas) and peripheral blood were used for the whole exome sequencing (bam files). Exons were narrowed down by using of SureSelect Human All Exon v.4 and read by Illumina HiSeq 2000 (paired-end: 100 bp)"},"dataProviders":[{"name":{"ja":"斉藤 延人","en":"Nobuhito Saito"},"organization":{"name":{"ja":"東京大学 医学部 脳神経外科","en":"Department of Neurosurgery, The University of Tokyo"}}}],"researchProjects":[{"name":{"ja":"次世代がん研究シーズ戦略的育成プログラム/がん臨床シーズ育成グループ","en":"Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT)"},"url":{"ja":null,"en":null}}],"grants":[{"title":{"ja":"新規血管奇形原因遺伝子による疾患発症メカニズムの解明","en":"Analysis of novel vascular malformation causative gene"},"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":["21H03041"]},{"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/悪性脳腫瘍克服のための新規治療標的及びバイオマーカーの創出","en":"Development of novel therapeutic strategy and biomarker for the treatment of malignant brain tumors"},"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":null},{"title":{"ja":"神経膠腫(グリオーマ)の治療抵抗性に関連した不均一性獲得機構の解明とそれに対応する治療戦略の構築","en":"Analysis of the mechanisms for development of tumor heterogeneity related to treatment resistance of gliomas and discovery of therapeutic strategies"},"agency":{"ja":"日本医療研究開発機構（AMED） 次世代がん医療創生研究事業（P-CREATE）","en":"Project for Cancer Research and Therapeutic Evolution (P-CREATE), Japan Agency for Medical Research and Development (AMED)"},"grantIds":null}],"relatedPublications":[{"title":"Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma","doi":"https://doi.org/10.1126/science.1239947","datasets":["JGAD000004"]},{"title":"Genetic and epigenetic stability of oligodendrogliomas at recurrence","doi":"https://doi.org/10.1186/s40478-017-0422-z","datasets":["JGAD000106","JGAD000107","JGAD000108"]},{"title":"Distinct molecular profile of diffuse cerebellar gliomas","doi":"https://doi.org/10.1007/s00401-017-1771-1","datasets":["JGAD000112","JGAD000113","JGAD000114"]},{"title":"DNA demethylation is associated with malignant progression of lower-grade gliomas","doi":"https://doi.org/10.1038/s41598-019-38510-0","datasets":["JGAD000215","JGAD000216","JGAD000217","JGAD000218","JGAD000219"]},{"title":"Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations","doi":"https://doi.org/10.1007/s10456-022-09846-5","datasets":["JGAD000436"]}],"datasets":["JGAD000004","JGAD000106","JGAD000107","JGAD000108"],"controlledAccessUsers":[{"principalInvestigator":{"en":"Nehemiah Alvarez"},"affiliation":{"en":"De Novo Genomics Corporation"},"country":{"ja":"アメリカ合衆国 (カンザス州)","en":"Kansas, United States"},"researchTitle":{"ja":"Evolutionary conservation of gene expression and epigenetic analysis of  trophoblast stem cells","en":"Evolutionary conservation of gene expression and epigenetic analysis of  trophoblast stem cells"},"periodStart":"2018-01-15","periodEnd":"2021-03-19","datasets":["JGAD000112"]},{"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":["JGAD000107","JGAD000113","JGAD000216","JGAD000219"]},{"principalInvestigator":{"en":"Frank Attenello"},"affiliation":{"en":"Department of Neurological Surgery, USC Keck School of Medicine"},"country":{"ja":"アメリカ合衆国","en":"United States"},"researchTitle":{"en":"Examining the role of a novel long noncoding RNA, linc02454, in resistance of glioblastoma to temozolomide"},"periodStart":"2023-04-06","periodEnd":"2026-01-31","datasets":["JGAD000215","JGAD000216","JGAD000217","JGAD000218","JGAD000219"]}]}