Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Cancer Cell. 2016 May 9;29(5):723-736. doi: 10.1016/j.ccell.2016.04.002.

Abstract

We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / pathology
  • Adrenal Cortex Neoplasms / therapy
  • Adrenocortical Carcinoma / genetics*
  • Adrenocortical Carcinoma / pathology
  • Adrenocortical Carcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • DNA Methylation
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease / genetics
  • Genome, Human / genetics*
  • Genomics / methods*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Outcome Assessment, Health Care
  • Prognosis
  • Young Adult