{"id":"hum0276","version":1,"url":"https://humandbs.dbcls.jp/research/hum0276/v1","datePublished":"2021-10-01","versions":[{"version":1,"datePublished":"2021-10-01"}],"title":{"ja":"Gorlin症候群に対する汎用型遺伝子診断パネルの開発とリキッドバイオプシーへの応用","en":"Development of a general-purpose genetic diagnostic panel for Gorlin syndrome and its application to liquid biopsy"},"summary":{"aims":{"ja":"Gorlin症候群の特徴は、顎骨に多発する歯原性角化嚢胞や皮膚に生じる基底細胞癌であり、本疾患の原因遺伝子はPTCH1である。本疾患は根本的な治療薬が無く、各症状で発症年齢に違いがあるため、経時的な診察により早期診断と治療が求められる。以上の点から、本疾患の病態解明を行うとともにGorlin症候群に対する汎用型遺伝子診断パネルを作製し、以下の内容を検証する。①Gorlin症候群の責任遺伝子となりうる4遺伝子（PTCH1、PTCH2、SMO、SUFU）におけるゲノム変異検出可能な汎用型遺伝子診断パネル検査の有用性の検証。②血液、口腔組織、嚢胞から採取した検体からゲノムDNAを抽出し、次世代シークエンサーでの解析を行うことで、病理検体採取よりも侵襲度の低い血液検体を対象とした遺伝子診断パネルの有用性の検証、並びに、組織由来DNAと同様の結果が血液より得られるかの検証。","en":"The responsible gene for Gorlin syndrome is PTCH1. Early diagnosis by genetic testing is necessary. In this study, we will create a generic genetic diagnostic panel for Gorlin syndrome. The following points will be verified. (1) To validate the usefulness of a general-purpose genetic diagnostic panel test that can detect genomic mutations in the four genes (PTCH1, PTCH2, SMO, and SUFU) that are thought to cause Gorlin syndrome. (2) Extract genomic DNA from peripheral blood samples, oral tissues, and cysts and analyze them with a next-generation sequencer to verify the usefulness of a genetic diagnostic panel test from blood samples, which is less invasive than pathological specimen collection, and whether the same results can be obtained from blood-derived DNA as from tissue-derived DNA."},"methods":{"ja":"本研究への参加に同意されたGorlin症候群患者のうち、2014年10月から2025年3月の期間に手術摘出組織の一部、口腔組織、および血液からDNAを抽出する。同様に、本研究への参加に同意されたGorlin症候群患者の血縁者が、他の疾患の診断を目的とした場合や全身麻酔の術前検査で必要となった場合の採取の残血からDNAを抽出する。抽出したDNAのライブラリー調整後に次世代シークエンサー解析にかけ、解析結果から本疾患の原因となりうる4遺伝子（PTCH1、PTCH2、SMO、SUFU）の変異解析を行う。","en":"Genomic DNA is extracted from a portion of tissues, oral tissues, and blood samples removed during surgery between October 2014 and March 2025 from patients with Gorlin syndrome who have given consent for this study. Similarly, genomic DNA is extracted from leftover blood samples taken by blood relatives of patients with Gorlin syndrome who have consented to participate in this study, when needed for the purpose of diagnosing other diseases or for preoperative testing for general anesthesia. Libraries are prepared from the extracted DNAs and they are subjected to the next-generation sequencing analysis. Four genes (PTCH1, PTCH2, SMO, and SUFU) that may cause the disease are targeted and mutation analysis was performed."},"targets":{"ja":"研究対象者は東京歯科大学千葉歯科医療センター、水道橋病院、市川総合病院で治療を行っているGorlin症候群患者で本研究に参加同意された方と未診断の患者の血縁者。","en":"The research subjects are patients with Gorlin syndrome treated at the Chiba Dental Center of the Tokyo Dental University, Suidobashi Hospital, and Ichikawa General Hospital who have consented to participate in this study, and undiagnosed blood relatives."},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"配列決定","en":"Sequencing"},"targets":{"ja":"Gorlin症候群：12症例\n血縁者：3名\n（日本人）","en":"12 patients with Gorlin syndrome\n3 blood relatives\n(Japanese)"},"typeOfData":{"ja":"NGS\n（Target Capture）","en":"NGS\n(Target Capture)"}},"releaseNote":{"ja":"Gorlin症候群患者の病変組織（嚢胞）および正常組織（歯肉、血液）、並びに、血縁者の血液から抽出したgDNAを用いた4遺伝子（PTCH1、PTCH2、SMO、SUFU）のTarget Capture Sequencing解析データをfastqおよびbamファイルにて提供する。","en":"gDNA extracted from cysts, gingival, and blood samples of 12 patients with Gorlin syndrome, and blood samples of 3 blood relatives were used for the target capture sequencing analysis. Fastq and bam files are provided."},"dataProviders":[{"name":{"ja":"東 俊文","en":"Toshifumi Azuma"},"organization":{"name":{"ja":"東京歯科大学 生化学講座","en":"Department of Biochemistry, Tokyo Dental College"}}}],"researchProjects":[{"name":{"ja":"私立大学研究ブランディング事業 顎骨疾患プロジェクト","en":"Tokyo dental College Research Branding Project"},"url":{"ja":[{"url":"https://www.tdc.ac.jp/research/projects/branding/","text":"https://www.tdc.ac.jp/research/projects/branding/"}],"en":null}}],"grants":[{"title":{"ja":"Gorlin症候群由来iPS細胞を用いた歯原性角化嚢胞モデルの樹立とその応用","en":"Establishment and application of an odontogenic keratocyst model using Gorlin syndrome-derived iPS cells"},"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":["18K09753"]},{"title":{"ja":"疾患iPS細胞を用いたGNAS-cAMP経路の骨芽細胞分化石灰化メカニズム解明","en":"The osteoblast differentiation and calcification mechanism of GNAS-cAMP pathway using diseased iPS cells"},"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":["18H03007"]},{"title":{"ja":"リキッドバイオプシーで応用可能なGorlin症候群診断遺伝子パネルの開発","en":"Development of a diagnostic gene panel for Gorlin syndrome that can be applied in liquid biopsy"},"agency":{"ja":"東京歯科大学研究ブランディング事業大学院研究助成","en":"Tokyo dental College Research Branding Project"},"grantIds":null}],"relatedPublications":[],"datasets":["JGAD000419"],"controlledAccessUsers":[{"principalInvestigator":{"ja":"湯原 悟志","en":"Satoshi Yuhara"},"affiliation":{"ja":"研究開発本部　試験開発部　バイオインフォマティクス課, 株式会社エスアールエル","en":"SRL inc./ H.U. Group Research Institute G.K."},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"希少疾患クリニカルレポーティングシステムの検証","en":"Validation of Rare Disease Clinical Reporting System"},"periodStart":"2024-07-01","periodEnd":"2026-07-01","datasets":["JGAD000419"]}]}