• Open Access

Somatic mutations in the chromatin remodeling gene ARID1A occur in several tumor types

Authors

  • Siân Jones,

    1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland
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  • Meng Li,

    1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland
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  • D. Williams Parsons,

    1. Texas Children's Cancer Center and Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Xiaosong Zhang,

    1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland
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  • Jelle Wesseling,

    1. Department of Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital Plesmanlaan 121, Amsterdam, The Netherlands
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  • Petra Kristel,

    1. Department of Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital Plesmanlaan 121, Amsterdam, The Netherlands
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  • Marjanka K. Schmidt,

    1. Department of Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital Plesmanlaan 121, Amsterdam, The Netherlands
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  • Sanford Markowitz,

    1. Department of Medicine, and Seidman Cancer Center at Case Western Reserve University and Case Medical Center of University Hospitals of Cleveland, Cleveland, Ohio
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  • Hai Yan,

    1. Department of Pathology, Pediatric Brain Tumor Foundation, and Preston Robert Tisch Brain Tumor Center at Duke University Medical Center, Durham, North Carolina
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  • Darell Bigner,

    1. Department of Pathology, Pediatric Brain Tumor Foundation, and Preston Robert Tisch Brain Tumor Center at Duke University Medical Center, Durham, North Carolina
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  • Ralph H. Hruban,

    1. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • James R. Eshleman,

    1. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Christine A. Iacobuzio-Donahue,

    1. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Michael Goggins,

    1. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Anirban Maitra,

    1. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Sami N. Malek,

    1. Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
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  • Steve Powell,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia
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  • Bert Vogelstein,

    Corresponding author
    1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland
    • The Sidney Kimmel Comprehensive Cancer Center, Room 589, 1650 Orleans Street, Baltimore, MD 21231
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  • Kenneth W. Kinzler,

    1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland
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  • Victor E. Velculescu,

    1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland
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  • Nickolas Papadopoulos

    1. Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland
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  • Communicated by Ian N.M. Day

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. Hum Mutat 33:100–103, 2012. © 2011 Wiley Periodicals, Inc.

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