PT  - JOURNAL ARTICLE
AU  - Jones, Siân
AU  - Wang, Tian-Li
AU  - Shih, Ie-Ming
AU  - Mao, Tsui-Lien
AU  - Nakayama, Kentaro
AU  - Roden, Richard
AU  - Glas, Ruth
AU  - Slamon, Dennis
AU  - Diaz, Luis A.
AU  - Vogelstein, Bert
AU  - Kinzler, Kenneth W.
AU  - Velculescu, Victor E.
AU  - Papadopoulos, Nickolas
TI  - Frequent Mutations of Chromatin Remodeling Gene <em>ARID1A</em> in Ovarian Clear Cell Carcinoma
AID  - 10.1126/science.1196333
DP  - 2010 Oct 08
TA  - Science
PG  - 228--231
VI  - 330
IP  - 6001
4099  - http://science.sciencemag.org/content/330/6001/228.short
4100  - http://science.sciencemag.org/content/330/6001/228.full
SO  - Science2010 Oct 08; 330
AB  - Ovarian clear cell carcinoma (OCCC) is an aggressive human cancer that is generally resistant to therapy. To explore the genetic origin of OCCC, we determined the exomic sequences of eight tumors after immunoaffinity purification of cancer cells. Through comparative analyses of normal cells from the same patients, we identified four genes that were mutated in at least two tumors. PIK3CA, which encodes a subunit of phosphatidylinositol-3 kinase, and KRAS, which encodes a well-known oncoprotein, had previously been implicated in OCCC. The other two mutated genes were previously unknown to be involved in OCCC: PPP2R1A encodes a regulatory subunit of serine/threonine phosphatase 2, and ARID1A encodes adenine-thymine (AT)–rich interactive domain–containing protein 1A, which participates in chromatin remodeling. The nature and pattern of the mutations suggest that PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor gene. In a total of 42 OCCCs, 7% had mutations in PPP2R1A and 57% had mutations in ARID1A. These results suggest that aberrant chromatin remodeling contributes to the pathogenesis of OCCC.