2010年10月8日金曜日

卵巣明細胞癌で6割変異する遺伝子:サイエンスより

卵巣明細胞癌という癌は下に示すようにあまり予後の良くない癌らしい。(元来卵巣がんそのものの予後も不良なのだが)その明細胞癌の6割弱に変異が認められる遺伝子が見つかった。ARID1Aといってクロマチンのリモデリング関連遺伝子のようだ。6割とはは高頻度である。42例中24例で57%。ボーゲルシュタインのグループである。

Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma


Siân Jones,1 Tian-Li Wang,2 Ie-Ming Shih,3 Tsui-Lien Mao,4 Kentaro Nakayama,5 Richard Roden,3 Ruth Glas,6 Dennis Slamon,6 Luis A. Diaz, Jr.,1 Bert Vogelstein,1 Kenneth W. Kinzler,1,* Victor E. Velculescu,1,* Nickolas Papadopoulos1,*

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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