Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma
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.
Originally published in Science Express on 8 September 2010
Science 8 October 2010:
Vol. 330. no. 6001, pp. 228 - 231
大阪医療センターHPからのデータ
表層上皮性卵巣がんの組織型別の治療成績(1993-95)
組織型 | 臨床進行期 | |||||||
l期 | ll期 | lll期 | lV期 | |||||
例数 | 生存率 | 例数 | 生存率 | 例数 | 生存率 | 例数 | 生存率 | |
漿液性腺がん | 427 | 89.4 | 153 | 65.4 | 1188 | 32.7 | 254 | 18.5 |
粘液性腺がん | 477 | 90.7 | 44 | 78.7 | 149 | 38.0 | 38 | 12.3 |
類内膜腺がん | 228 | 87.0 | 82 | 69.1 | 208 | 37.6 | 46 | 24.6 |
明細胞腺がん | 101 | 83.6 | 27 | 63.5 | 68 | 27.4 | 15 | 0 |
未分化腺がん | 56 | 81.0 | 19 | 49.8 | 103 | 29.8 | 40 | 0 |
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