ENDOCRINE TUMOURS: The genomics of adrenocortical tumors.

Abstract : The last decade witnessed the emergence of genomics, a set of high-throughput molecular measurements in biological samples. These pan-genomic and agnostic approaches have revolutionized the molecular biology and genetics of malignant and benign tumors. These techniques have been applied successfully to adrenocortical tumors. Exome sequencing identified new major drivers in all tumor types, including KCNJ5, ATP1A1, ATP2B3 and CACNA1D mutations in aldosterone producing adenomas (APA), PRKACA mutations in cortisol producing adenomas (CPA), ARMC5 mutations in primary bilateral macronodular adrenocortical hyperplasia (PBMAH), and ZNRF3 mutations in adrenocortical carcinomas (ACC). Moreover, the various genomic approaches -including exome sequencing, transcriptome, miRNome, genome, and methylome-, converge into a single molecular classification of adrenocortical tumors. Especially for ACC, two main molecular groups have emerged, showing major differences in outcomes. These ACC groups differ by their gene expression profiles, but also by recurrent mutations and specific DNA hypermethylation patterns in the subgroup of poor outcome. The clinical impact of these findings is just starting. The main altered signaling pathways now become therapeutic targets. The molecular groups of diseases individualize robust subtypes within diseases such as APA, CPA, PBMAH and ACC. A revised nosology of adrenocortical tumors should impact the clinical research. Obvious consequences also include genetic counseling for the new genetic diseases such as ARMC5 mutations in PBMAH, and a better prognostication of ACC based on targeted measurements of a few discriminant molecular alterations. Identifying the main molecular groups of adrenocortical tumors by extensively gathering the molecular variations is a significant step forward towards precision medicine.
Type de document :
Pré-publication, Document de travail
2016
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  • HAL Id : inserm-01291562, version 1
  • PUBMED : 26739091

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Simon Faillot, Guillaume Assié. ENDOCRINE TUMOURS: The genomics of adrenocortical tumors.. 2016. 〈inserm-01291562〉

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