TY - JOUR
T1 - Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas
AU - Castro-Vega, Luis Jaime
AU - Letouzé, Eric
AU - Burnichon, Nelly
AU - Buffet, Alexandre
AU - Disderot, Pierre Hélie
AU - Khalifa, Emmanuel
AU - Loriot, Céline
AU - Elarouci, Nabila
AU - Morin, Aurélie
AU - Menara, Mélanie
AU - Lepoutre-Lussey, Charlotte
AU - Badoual, Cécile
AU - Sibony, Mathilde
AU - Dousset, Bertrand
AU - Libé, Rossella
AU - Zinzindohoue, Franck
AU - Plouin, Pierre François
AU - Bertherat, Jérôme
AU - Amar, Laurence
AU - De Reyniès, Aurélien
AU - Favier, Judith
AU - Gimenez-Roqueplo, Anne Paule
N1 - Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84923072111&partnerID=8YFLogxK
U2 - 10.1038/ncomms7044
DO - 10.1038/ncomms7044
M3 - Article
C2 - 25625332
AN - SCOPUS:84923072111
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 6044
ER -