Somatic mutations in the chromatin remodeling gene ARID1A occur in several tumor types.
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.
Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA.
Siân
S
Jones
Meng
M
Li
D Williams
DW
Parsons
Xiaosong
X
Zhang
Jelle
J
Wesseling
Petra
P
Kristel
Marjanka K
MK
Schmidt
Sanford
S
Markowitz
Hai
H
Yan
Darell
D
Bigner
Ralph H
RH
Hruban
James R
JR
Eshleman
Christine A
CA
Iacobuzio-Donahue
Michael
M
Goggins
Anirban
A
Maitra
Sami N
SN
Malek
Steve
S
Powell
Bert
B
Vogelstein
Kenneth W
KW
Kinzler
Victor E
VE
Velculescu
Nickolas
N
Papadopoulos
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D001940:Breast / Q000378:metabolism / Q000473:pathology; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D016368:Frameshift Mutation; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
C112476:ARID1A protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors