Integrative Molecular Characterization of Malignant Pleural Mesothelioma.
Integrative Molecular Characterization of Malignant Pleural Mesothelioma.
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DOI：
10.1158/2159-8290.cd-18-0804
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发表时间：
2018-12
期刊：
影响因子：
28.2
通讯作者：
Ladanyi M
中科院分区：
文献类型：
--
作者：
Hmeljak J;Sanchez-Vega F;Hoadley KA;Shih J;Stewart C;Heiman D;Tarpey P;Danilova L;Drill E;Gibb EA;Bowlby R;Kanchi R;Osmanbeyoglu HU;Sekido Y;Takeshita J;Newton Y;Graim K;Gupta M;Gay CM;Diao L;Gibbs DL;Thorsson V;Iype L;Kantheti H;Severson DT;Ravegnini G;Desmeules P;Jungbluth AA;Travis WD;Dacic S;Chirieac LR;Galateau-Sallé F;Fujimoto J;Husain AN;Silveira HC;Rusch VW;Rintoul RC;Pass H;Kindler H;Zauderer MG;Kwiatkowski DJ;Bueno R;Tsao AS;Creaney J;Lichtenberg T;Leraas K;Bowen J;TCGA Research Network;Felau I;Zenklusen JC;Akbani R;Cherniack AD;Byers LA;Noble MS;Fletcher JA;Robertson AG;Shen R;Aburatani H;Robinson BW;Campbell P;Ladanyi M
恶性胸膜间皮瘤（MPM）是胸腔内膜的高度致命癌。为了扩展我们对MPM的理解，我们进行了一项全面的综合基因组研究，包括迄今为止对BAP1改变的最详细分析。我们确定了与组织学无关的分子预后子集，并定义了具有TP53和SETDB1突变的新型基因组亚型以及杂合性的广泛丧失。我们还报告了上皮样MPM中免疫检查点基因远景的强烈表达，比其他固体癌症高得多，这对对MPM的免疫反应及其免疫疗法有影响。我们的发现突出了新的途径，以进一步研究MPM生物学和新型治疗选择。
Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options.