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

Luis Jaime Castro-Vega, Eric Letouzé, Nelly Burnichon, Alexandre Buffet, Pierre Hélie Disderot, Emmanuel Khalifa, Céline Loriot, Nabila Elarouci, Aurélie Morin, Mélanie Menara, Charlotte Lepoutre-Lussey, Cécile Badoual, Mathilde Sibony, Bertrand Dousset, Rossella Libé, Franck Zinzindohoue, Pierre François Plouin, Jérôme Bertherat, Laurence Amar, Aurélien De ReynièsJudith Favier, Anne Paule Gimenez-Roqueplo

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

153 Citations (Scopus)

Résumé

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.

langue originaleAnglais
Numéro d'article6044
journalNature Communications
Volume6
Les DOIs
étatPublié - 1 janv. 2015
Modification externeOui

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