Somatic mutations in the chromatin remodeling gene <i>ARID1A</i> occur in several tumor types

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.

Keywords

Affiliated Institutions

• Pediatric Brain Tumor Foundation US
• The Netherlands Cancer Institute NL
• Children's Cancer Center US
• Duke Medical Center US
• University of Virginia Health System US
• University Hospitals Seidman Cancer Center US
• University of Michigan US
• University Hospitals of Cleveland US
• Case Western Reserve University US
• Sidney Kimmel Cancer Center US
• Johns Hopkins University US
• Howard Hughes Medical Institute US
• Cancer Genetics (United States) US
• Baylor College of Medicine US
• Cancer Research Center US

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