Exomic sequences of ovarian clear cell carcinomas

Ovarian Clear Cell Carcinoma (OCCC) is an aggressive cancer that is generally resistant to therapy. To gain novel insights into the genetic origin of this tumor type, we determined the exomic sequences of eight tumors after immunoaffinity purification of neoplastic cells. Through comparison to normal cells from the same patients, we identified four genes that were mutated in at least two tumors. Two of these were known to play a role in this tumor type (PIK3CA and KRAS) and two were novel: the serine/threonine phosphatase gene PPP2R1A and the chromatin remodeling gene ARID1A. Recurrent missense mutations at codons 182 and 183 of PPP2R1A suggested it was an oncogene while truncating mutations throughout the ARID1A gene suggested it encoded an OCCC tumor suppressor. In 42 OCCCs, 7% contained mutations in PPP2R1A and 57% had mutations in ARID1A. These results provide new insights into the pathogenesis of OCCC cancers and suggest that aberrant chromatin remodeling plays a central role in the process.
US Patent 9,982,304 issued May 29, 2018

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