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

Citations Over TimeTop 1% of 2015 papers

Abstract

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.

Related Papers

• → Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan(1996)502 cited
• → Differences between germline and somatic mutation rates in humans and mice(2017)431 cited
• → The mutational landscape of human somatic and germline cells(2022)13 cited
• → Germline mutations in the Von Hippel‐Lindau disease (VHL) gene in families from North America, Europe, and Japan(1996)42 cited
• → 28. Identification of TP53 germline variants in pediatric patients undergoing tumor testing(2022)