Integrated Genomics for Pinpointing Survival Loci within Arm-Level Somatic Copy Number Alterations

Cancer Cell. 2016 May 9;29(5):737-750. doi: 10.1016/j.ccell.2016.03.025.

Abstract

The identification of driver loci underlying arm-level somatic copy number alterations (SCNAs) in cancer has remained challenging and incomplete. Here, we assess the relative impact and present a detailed landscape of arm-level SCNAs in 10,985 patient samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Furthermore, using chromosome 9p loss in lower grade glioma (LGG) as a model, we employ a unique multi-tiered genomic dissection strategy using 540 patients from three independent LGG datasets to identify genetic loci that govern tumor aggressiveness and poor survival. This comprehensive approach uncovered several 9p loss-specific prognostic markers, validated existing ones, and redefined the impact of CDKN2A loss in LGG.

Publication types

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

MeSH terms

  • Chromosome Deletion
  • Chromosomes, Human, Pair 9 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • DNA Copy Number Variations*
  • DNA Methylation
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human / genetics*
  • Genomics / methods*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Prognosis
  • Survival Analysis

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18