Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas.
Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas.
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DOI：
10.1038/ncomms7044
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发表时间：
2015-01-27
影响因子：
16.6
通讯作者：
Gimenez-Roqueplo, Anne-Paule
中科院分区：
文献类型：
--
作者：
Castro-Vega, Luis Jaime;Letouze, Eric;Burnichon, Nelly;Buffet, Alexandre;Disderot, Pierre-Helie;Khalifa, Emmanuel;Loriot, Celine;Elarouci, Nabila;Morin, Aurelie;Menara, Melanie;Lepoutre-Lussey, Charlotte;Badoual, Cecile;Sibony, Mathilde;Dousset, Bertrand;Libe, Rossella;Zinzindohoue, Franck;Plouin, Pierre Francois;Bertherat, Jerome;Amar, Laurence;de Reynies, Aurelien;Favier, Judith;Gimenez-Roqueplo, Anne-Paule
嗜铬细胞瘤和副神经节瘤（PCCs/PGLs）是神经嵴源性肿瘤，具有很强的遗传成分。在这里，我们报告了第一次对大量PCC/PGL的综合基因组检查。SNP阵列分析揭示了与遗传背景相关的不同拷贝数模式。全外显子组测序显示每百万碱基0.3个突变的低突变率，在以前与PCC/PGL无关的基因中很少有复发性体细胞突变。DNA甲基化阵列和miRNA测序鉴定了与信使RNA表达谱密切相关的DNA甲基化变化和miRNA表达簇。miRNA集群182/96/183在sdhb突变的肿瘤中特异性表达，并诱导恶性性状，而印迹DLK1-MEG3 miRNA集群的沉默似乎是散发性肿瘤亚组的潜在驱动因素。总之，PCC/PGL的完整基因组景观主要由易感基因的不同种系和/或体细胞突变驱动，并显示出不同的分子实体，以一系列独特的基因组改变为特征。嗜铬细胞瘤和副神经节瘤（PCCs/PGLs）是罕见的神经内分泌肿瘤，具有重要的遗传成分。本研究中，作者对PCC/PGL进行了多组学综合表征，揭示了与该疾病相关的潜在基因组改变和调控机制。
Pheochromocytomas and paragangliomas (PCCs/PGLs) are neural crest-derived tumours with a very strong genetic component. Here we report the first integrated genomic examination of a large collection of PCC/PGL. SNP array analysis reveals distinct copy-number patterns associated with genetic background. Whole-exome sequencing shows a low mutation rate of 0.3 mutations per megabase, with few recurrent somatic mutations in genes not previously associated with PCC/PGL. DNA methylation arrays and miRNA sequencing identify DNA methylation changes and miRNA expression clusters strongly associated with messenger RNA expression profiling. Overexpression of the miRNA cluster 182/96/183 is specific in SDHB-mutated tumours and induces malignant traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster appears as a potential driver in a subgroup of sporadic tumours. Altogether, the complete genomic landscape of PCC/PGL is mainly driven by distinct germline and/or somatic mutations in susceptibility genes and reveals different molecular entities, characterized by a set of unique genomic alterations. Pheochromocytomas and paragangliomas (PCCs/PGLs) are rare neuroendocrine tumours with a significant genetic component. Here, the authors carry out a multi-omic integrative characterization of PCC/PGL and reveal potential genomic alterations and regulatory mechanisms involved in the disease.
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影响因子：
3.7
作者：
Favier, Judith;Briere, Jean-Jacques;Gimenez-Roqueplo, Anne-Paule
通讯作者：
Gimenez-Roqueplo, Anne-Paule
影响因子：
3.5
作者：
Castro-Vega, Luis Jaime;Buffet, Alexandre;Gimenez-Roqueplo, Anne-Paule
通讯作者：
Gimenez-Roqueplo, Anne-Paule
HIF1Alpha调节环将缺氧和线粒体信号联系起来。
影响因子：
4.5
作者：
Dahia, PLM;Ross, KN;Wright, ME;Hayashida, CY;Santagata, S;Barontini, M;Kung, AL;Sanso, G;Powers, JF;Tischler, AS;Hodin, R;Heitritter, S;Moore, F;Dluhy, R;Sosa, JA;Ocal, IT;Benn, DE;Marsh, DJ;Robinson, BG;Schneider, K;Garber, J;Arum, SM;Korbonits, M;Grossman, A;Pigny, P;Toledo, SPA;Nosé, V;Li, C;Stiles, CD
通讯作者：
Stiles, CD
影响因子：
28.2
作者：
Killian JK;Kim SY;Miettinen M;Smith C;Merino M;Tsokos M;Quezado M;Smith WI Jr;Jahromi MS;Xekouki P;Szarek E;Walker RL;Lasota J;Raffeld M;Klotzle B;Wang Z;Jones L;Zhu Y;Wang Y;Waterfall JJ;O'Sullivan MJ;Bibikova M;Pacak K;Stratakis C;Janeway KA;Schiffman JD;Fan JB;Helman L;Meltzer PS
通讯作者：
Meltzer PS
影响因子：
16.6
作者：
Huether, Robert;Dong, Li;Chen, Xiang;Wu, Gang;Parker, Matthew;Wei, Lei;Ma, Jing;Edmonson, Michael N.;Hedlund, Erin K.;Rusch, Michael C.;Shurtleff, Sheila A.;Mulder, Heather L.;Boggs, Kristy;Vadordaria, Bhavin;Cheng, Jinjun;Yergeau, Donald;Song, Guangchun;Becksfort, Jared;Lemmon, Gordon;Weber, Catherine;Cai, Zhongling;Dang, Jinjun;Walsh, Michael;Gedman, Amanda L.;Faber, Zachary;Easton, John;Gruber, Tanja;Kriwacki, Richard W.;Partridge, Janet F.;Ding, Li;Wilson, Richard K.;Mardis, Elaine R.;Mullighan, Charles G.;Gilbertson, Richard J.;Baker, Suzanne J.;Zambetti, Gerard;Ellison, David W.;Zhang, Jinghui;Downing, James R.
通讯作者：
Downing, James R.