Somatic Mutations in the Chromatin Remodeling Gene ARID1A Occur in Several Tumor Types

Hum Mutat. 2012 Jan;33(1):100-3. doi: 10.1002/humu.21633. Epub 2011 Nov 23.

Abstract

Mutations in the chromatin remodeling gene ARID1A have recently been identified in the majority of ovarian clear cell carcinomas (OCCCs). To determine the prevalence of mutations in other tumor types, we evaluated 759 malignant neoplasms including those of the pancreas, breast, colon, stomach, lung, prostate, brain, and blood (leukemias). We identified truncating mutations in 6% of the neoplasms studied; nontruncating somatic mutations were identified in an additional 0.4% of neoplasms. Mutations were most commonly found in gastrointestinal samples with 12 of 119 (10%) colorectal and 10 of 100 (10%) gastric neoplasms, respectively, harboring changes. More than half of the mutated colorectal and gastric cancers displayed microsatellite instability (MSI) and the mutations in these tumors were out-of-frame insertions or deletions at mononucleotide repeats. Mutations were also identified in 2-8% of tumors of the pancreas, breast, brain (medulloblastomas), prostate, and lung, and none of these tumors displayed MSI. These findings suggest that the aberrant chromatin remodeling consequent to ARID1A inactivation contributes to a variety of different types of neoplasms.

Publication types

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

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / pathology
  • Base Sequence
  • Breast / metabolism
  • Breast / pathology
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Frameshift Mutation*
  • Gastric Mucosa / metabolism
  • Humans
  • Male
  • Microsatellite Instability
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Stomach / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Transcription Factors / genetics*

Substances

  • ARID1A protein, human
  • Chromatin
  • Nuclear Proteins
  • Transcription Factors