Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas

被引：151

作者：

Castro-Vega, Luis Jaime ^{[1
,2
]}

Letouze, Eric ^{[3
]}

Burnichon, Nelly ^{[1
,2
,4
]}

Buffet, Alexandre ^{[1
,2
,4
]}

Disderot, Pierre-Helie ^{[1
,2
]}

Khalifa, Emmanuel ^{[1
,2
,4
]}

Loriot, Celine ^{[1
,2
]}

Elarouci, Nabila ^{[3
]}

Morin, Aurelie ^{[1
,2
]}

Menara, Melanie ^{[1
,2
]}

Lepoutre-Lussey, Charlotte ^{[1
,2
,5
]}

Badoual, Cecile ^{[1
,2
,6
]}

Sibony, Mathilde ^{[2
,7
]}

Dousset, Bertrand ^{[2
,8
,9
,10
]}

Libe, Rossella ^{[2
,9
,10
,11
,12
]}

Zinzindohoue, Franck ^{[2
,13
]}

Plouin, Pierre Francois ^{[1
,2
,5
,12
]}

Bertherat, Jerome ^{[2
,9
,10
,11
,12
]}

Amar, Laurence ^{[1
,2
,5
]}

de Reynies, Aurelien ^{[3
]}

Favier, Judith ^{[1
,2
]}

Gimenez-Roqueplo, Anne-Paule ^{[1
,2
,4
,12
]}

机构：

[1] INSERM, UMR970, Paris Cardiovasc Res Ctr, F-75015 Paris, France

[2] Univ Paris 05, Sorbonne Paris Cite, Fac Med, F-75006 Paris, France

[3] Ligue Natl Canc, Programme Cartes Identite Tumeurs, F-75013 Paris, France

[4] Hop Europe Georges Pompidou, AP HP, Dept Genet, F-75015 Paris, France

[5] Hop Europe Georges Pompidou, AP HP, Hypertens Unit, F-75015 Paris, France

[6] Hop Europe Georges Pompidou, AP HP, Dept Pathol, F-75015 Paris, France

[7] Hop Cochin, AP HP, Dept Pathol, F-75006 Paris, France

[8] Hop Cochin, AP HP, Dept Digest & Endocrine Surg, F-75006 Paris, France

[9] INSERM, U1016, Inst Cochin, F-75006 Paris, France

[10] CNRS, UMR8104, F-75006 Paris, France

[11] Hop Cochin, AP HP, Dept Endocrinol, F-75006 Paris, France

[12] Rare Adrenal Canc Network COMETE, F-75006 Paris, France

[13] Hop Europe Georges Pompidou, AP HP, Dept Surg, F-75015 Paris, France

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

MALIGNANT PHEOCHROMOCYTOMAS; SOMATIC MUTATIONS; EXPRESSION PROFILES; GENETIC LANDSCAPE; DRIVER MUTATIONS; SDHB GENE; H-RAS; CANCER; BENIGN; MICRORNAS;

D O I：

10.1038/ncomms7044

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

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