{"id":"hum0335","version":1,"url":"https://humandbs.dbcls.jp/research/hum0335/v1","datePublished":"2022-09-14","versions":[{"version":1,"datePublished":"2022-09-14"}],"title":{"ja":"遺伝子解析と免疫形質を組み合わせたリンパ増殖性疾患の新たな診断と臨床像の調査研究","en":"Research on new diagnosis and clinical picture of lymphoproliferative diseases by combining genetic analysis and immunological traits"},"summary":{"aims":{"ja":"急性リンパ性白血病、悪性リンパ腫、慢性リンパ性白血病、多発性骨髄腫などを含むリンパ増殖性疾患は、典型例を除きその診断は病理学的にも困難なことは稀ではなく、染色体分析や免疫形質、遺伝子異常を加味した診断が以前から行われている。近年の遺伝子異常に関する網羅的解析や免疫学的研究の進歩から、診断に結びつく新たな異常や特徴が続々と報告されているが、実臨床における診断はそうした変化に追いついていないのが現状である。現在リンパ増殖性疾患の診断は、2017年に発表されたWHO分類に基づいて行われているが、その中にもすでに実臨床の中に取り入れることができていない遺伝子検査や免疫形質の検査が多く盛り込まれている。そこで通常診療で行われていない遺伝子変異を網羅的に解析し、免疫形質の分析を行うことで得られた新たな診断と現状の病理診断における生命予後を含めた臨床像を比較検討する。","en":"Diagnosis of lymphoproliferative diseases, except for typical cases, is often pathologically difficult, and diagnosis has long been based on chromosome analysis, immunological traits, and genetic abnormalities. Recent advances in the comprehensive analysis of genetic abnormalities and immunological studies have led to a number of reports of new abnormalities and features that can lead to diagnosis, but diagnosis in clinical practice has not kept pace with these changes. In this study, we compared the clinical picture, including prognosis, of the current pathological diagnosis with that of a new diagnosis based on comprehensive analysis of genetic mutations and immunological traits that have not yet been incorporated into conventional clinical practice."},"methods":{"ja":"ARID1A、NOTCH2、CXCR4、MYD88、PRDM1、CD274、PDCD1LG2、RAG2、KMT2D、MYBBP1A、TP53、CD79B のコーディング領域をカバーするプライマーを作成し、次世代シーケンサー（NextSeq 500）を使用したターゲットシーケンスを行った。GRCh37/hg19に基づいてアノテーションを行った後、以下の条件に該当する変異を除外した。Read Depth<500、Alt Variant Freq<5%（MYD88 L265Pは<1%）、global freq>1%または1000 Genomes ProjectにおいてEast Asian pop freq>1%、synonymous mutations、inflame mutations、SIFTが\"tolerated\"またはPolyPhenが\"benign\"のmissense mutations","en":"We created primers covering the coding regions of ARID1A, NOTCH2, CXCR4, MYD88, PRDM1, CD274, PDCD1LG2, RAG2, KMT2D, MYBBP1A, TP53, and CD79B and performed targeted sequencing using the NextSeq 500 next-generation sequencer. After annotation based on GRCh37/hg19, mutations that met the following criteria were filtered out: Read Depth < 500, Alt Variant Freq < 5% (< 1% on MYD88 L265P), global frequency > 1% or East Asian pop frequency > 1% based on 1000 Genomes Project, synonymous mutations, inflame mutations, and missense mutations scored \"tolerated\" by SIFT or \"benign\" by PolyPhen."},"targets":{"ja":"原発性マクログロブリン血症（Waldenström macroglobulinemia：WM）10症例およびnon IgM-typeリンパ形質細胞性リンパ腫 （lymphoplasmacytic lymphoma：LPL）10症例の各種検体から抽出したDNA","en":"DNAs extracted from specimens from 10 cases of Waldenström macroglobulinemia and 10 cases of non IgM-type lymphoplasmacytic lymphoma (LPL)"},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"配列決定","en":"Sequencing"},"targets":{"ja":"原発性マクログロブリン血症：10症例\nnon IgM-type リンパ形質細胞性リンパ腫：10症例\n（日本人）","en":"Waldenström macroglobulinemia: 10 cases\nnon IgM-type lymphoplasmacytic lymphoma: 10 cases\n(Japanese)"},"typeOfData":{"ja":"NGS\n（Target Capture）","en":"NGS\n(Target Capture)"}},"releaseNote":{"ja":"原発性マクログロブリン血症10症例およびnon IgM-type リンパ形質細胞性リンパ腫10症例の骨髄単核球、末梢血単核球、骨髄FFPE検体およびリンパ節FFPE検体から抽出したDNAを用いた12遺伝子領域のTarget Capture seq解析データをbamファイルにて提供する。","en":"DNAs extracted from 10 cases of Waldenström macroglobulinemia and 10 cases of non IgM-type LPL were used for the target capture sequencing analysis using the NextSeq 500 next generation sequencer. Bam files are provided."},"dataProviders":[{"name":{"ja":"横濱 章彦","en":"Akihiko Yokohama"},"organization":{"name":{"ja":"群馬大学医学部附属病院 輸血部","en":"Division of Blood Transfusion Service, Gunma University"}}}],"researchProjects":[{"name":{"ja":"「Waldenström macroglobulinemia and non-IgM-type lymphoplasmacytic lymphoma are genetically similar」","en":"\"Waldenström macroglobulinemia and non-IgM-type lymphoplasmacytic lymphoma are genetically similar\""},"url":{"ja":null,"en":null}}],"grants":[{"title":{"ja":"悪性リンパ腫におけるアミノ酸トランスポーターの解析と治療への応用","en":"Amino acid transporter in malignant lymphoma; its analysis and clinical application"},"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":["16K10342"]}],"relatedPublications":[],"datasets":["DRA014819"],"controlledAccessUsers":[]}