{"id":"hum0041","version":1,"url":"https://humandbs.dbcls.jp/research/hum0041/v1","datePublished":"2017-01-12","versions":[{"version":1,"datePublished":"2017-01-12"}],"title":{"ja":"肝胆膵癌の早期発見、進行、予後予測、治療効果予測に関わる因子の研究","en":"Research of factors related to diagnosis, progression, prognosis and treatment of hepato-biliary-pancreatic malignancies"},"summary":{"aims":{"ja":"転移や再発を伴う進行がんの殆どは、依然として治療抵抗性があり、難治性がんである。肝がんの多施設検体コホートに基づく難治性規定分子の同定と分子標的治療の開発をテーマに、腫瘍組織および非腫瘍組織の全エキソン配列解析、網羅的エピゲノム解析、網羅的遺伝子発現解析を実施することにより、難治性肝がんを規定するドライバー遺伝子の候補を同定し、発がんメカニズム解析による新規治療法の開発、予防医学への応用を図る。","en":"Advanced cancers with metastasis and/or recurrence are usually resistant and refractory to treatment. In our studies, whole exome sequencing analysis, comprehensive epigenetic analysis and genome-wide expression analysis were performed using cancerous and non-cancerous tissues derived from multicentric cohort study of hepatocellular carcinoma (HCC). The aim of the studies is identification of the refractoriness-related deriver genes for application to novel molecular targeted therapy and preventive medicine."},"methods":{"ja":"難治性肝がんの指標には、ミラノ基準（基準外：腫瘍径5 cm以下単発腫瘍、または腫瘍径3 cm以内3個以内腫瘍、かつ遠隔転移・肉眼的脈管浸潤なし、基準内：少なくとも術後2年以内無再発）を用いた。主腫瘍組織、および周囲の非腫瘍組織からDNAを抽出し、Genome-Wide Human SNP Array 6.0（Affymetrix）を用いたSNP解析による検証を行った後、全エキソン配列解析を施行した。全エキソン配列解析は、BWAによるhg19リファレンスゲノムへのマッピング、およびGATKによるリアラインメント・リキャリブレーションを経て、VarScan、MuTect、SomaticIndelDetector、FATHMMなどを組み合わせたフィルター、およびIGVによる目視確認を経て、変異の選択を行った。","en":"The materials were obtained from thirty three patients underwent curative hepatectomy for HCC at Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University Hospital. Written informed consent from these patients, as well as the institutional review board approved was obtained. The determination of the refractory HCC group (16 cases) was based on the point of the recurrence patterns in accordance with Milan criteria for the recurrent tumor (solitary <5cm, or up to 3 nodules <3 cm, without major vascular invasion or distant metastasis) that has been proposed as the useful criteria of the liver transplantation for HCC. The cellular DNA was extracted from the cancerous and non-cancerous tissues of primary HCC by the phenol-chloroform method. After SNP certification using Genome-Wide Human SNP Array 6.0 (Affymetrix), whole exome sequencing was performed at the Cancer Institute of JFCR, as the support infrastructure. Exome sequencing was performed using HiSeq 2000 (Illumina), and the obtained reads were mapped to the human reference genome (hg19) using BWA software. GATK software was used for local realignment base call recalibration. Single nucleotide variants (SNVs) and indels were analyzed by VarScan, MuTect, SomaticIndelDetector and FATHMM software, as well as visual confirmation by IGV software."},"targets":{"ja":"難治性肝がんは高率に再発をきたす疾患であるが、再発しても治療可能なミラノ基準内の再発であれば再切除などで治癒可能であることが多いが、ミラノ基準外再発では治癒困難であり、しばしば致死的となる。本課題では、肝がんの致死的再発解明の観点から、根治的肝切除手術を施行した原発性肝細胞がん33症例（ミラノ基準外再発例16症例と基準内再発例17症例）の手術時切除切片（腫瘍組織及び非腫瘍組織）を用いた。","en":"The studies are intended for refractory HCC. High frequency of the tumor recurrence even after curative resection is one of the major difficulties in the treatment of HCC. According to our previous studies, not the recurrence itself, but the recurrence pattern has critical effects on prognosis of the patient with HCC. Then, we analyzed the cancerous and non-cancerous tissues of primary HCC on the point of the recurrence patterns in accordance with or without Milan criteria."},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"配列決定","en":"Sequencing"},"targets":{"ja":"原発性肝細胞癌：33症例\n（日本人）","en":"33 primary HCC\n(Japanese)"},"typeOfData":{"ja":"NGS\n（Exome、Target Capture）","en":"NGS\n(Exome, Target Capture)"}},"releaseNote":{"ja":"原発性肝細胞がん33症例の腫瘍組織および非腫瘍組織から抽出したDNAを使用したExome解析（SureSelect）およびHBVとlincRNAのtarget capture解析の結果をFastqファイルで提供する。SureSelect Human All Exon V4にて平均長200 塩基を解読した（Paired-end）。","en":"gDNA extracted from cancerous and non-cancerous tissues derived from 33 patients with refractory hepatocellular carcinoma (HCC) were used for whole exome sequencing analysis (fastq files).\nSureSelect Human All Exon V4 was used for preparing libraries and read by Illumina HiSeq 2000 (paired-end, 2 x 100 bp)."},"dataProviders":[{"name":{"ja":"田中 真二","en":"Shinji Tanaka"},"organization":{"name":{"ja":"東京医科歯科大学大学院 医歯学総合研究科（医系） 分子腫瘍医学分野","en":"Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University"}}}],"researchProjects":[{"name":{"ja":"次世代がん研究シーズ戦略的育成プログラム「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」","en":"Project for Development of Innovative Research on Cancer Therapeutics"},"url":{"ja":[{"url":"https://www.tmd.ac.jp/grad/monc/index.html","text":"https://www.tmd.ac.jp/grad/monc/index.html"}],"en":[{"url":"https://www.tmd.ac.jp/grad/monc/en/index.html","text":"https://www.tmd.ac.jp/grad/monc/en/index.html"}]}}],"grants":[{"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」（肝がんの多施設検体コホートに基づく難治性規定分子の同定と分子標的治療の開発）","en":"Development of the Intractable Cancer Therapies through the New Target Identification by the Molecular Profiling"},"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":["JP15cm0106064"]}],"relatedPublications":[],"datasets":["JGAD000052"],"controlledAccessUsers":[]}