Transcriptomics

Dataset Information

298

MiRNA sequencing of pheochromocytomas (172 samples)


ABSTRACT: A Carte d'Identitite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net): Pheochromocytomas (PCC) and paragangliomas (PGL) are neural crest-derived tumors. We performed the integrated genomic analysis of a collection of PCC/PGL from the French COMETE network using SNP arrays, whole-exome sequencing, DNA methylation arrays, mRNA expression arrays and miRNA sequencing. We found that PCC/PGL are characterized by a low mutation rate, with few recurrent somatic mutations and focal copy number alterations (CNAs). In contrast, we detected recurrent broad CNAs strongly associated with known molecular groups, often leading to the biallelic inactivation of the known susceptibility genes of PCC/PGL. We also identified DNA methylation changes and miRNA expression clusters strongly associated with molecular groups. Of note, overexpression of the miRNA cluster 182/96/183 is specific of SDHB-mutated tumors and induces invasive traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster due to a loss of heterozygosity of the 14q32.2 locus is a potential driver in a subset of sporadic tumors. This comprehensive analysis illustrates the functional interdependence between genomic and epigenomic dysregulations underlying PCC/PGL.

INSTRUMENT(S): Qiagen MinElute, Illumina Hiseq 2000

ORGANISM(S): Homo sapiens  

SUBMITTER: Nabila Elarouci  

PROVIDER: E-MTAB-2833 | ArrayExpress | 2015-02-02

SECONDARY ACCESSION(S): ERP008960

REPOSITORIES: ArrayExpress, ENA

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Publications


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 miRN  ...[more]

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