A landscape of driver mutations in melanoma Academic Article uri icon

Overview

MeSH Major

  • Genome-Wide Association Study
  • Melanoma
  • Mutagenesis
  • Ultraviolet Rays

abstract

  • Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic UV light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes (PPP6C, RAC1, SNX31, TACC1, STK19, and ARID2), three of which-RAC1, PPP6C, and STK19-harbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS/BRAF mutations. The landscape also clarified a mutational basis for RB and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis.

authors

publication date

  • July 20, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3600117

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2012.06.024

PubMed ID

  • 22817889

Additional Document Info

start page

  • 251

end page

  • 63

volume

  • 150

number

  • 2