研究人員最新報告稱,，DNA與蛋白質(zhì)一同被包裹的方式的某種改變可能會通過造成基因被錯誤地激活或關(guān)閉而促使一種罕見的卵巢癌的發(fā)展。
這一發(fā)現(xiàn)為不斷增加的證據(jù)增添了新的內(nèi)容,，即：與將基因組的某部分激活或關(guān)閉的化學(xué)反應(yīng)（稱作表觀遺傳控制）有關(guān)的蛋白質(zhì)在人類癌癥的發(fā)展上起一種關(guān)鍵性的作用,。 在本研究中，Sian Jones及其同事在卵巢透明細(xì)胞癌中尋找基因突變,。透明細(xì)胞癌是一種罕見但卻特別致命形式的卵巢癌,。 在被檢驗的42個腫瘤中，他們發(fā)現(xiàn)有57%的腫瘤含有將ARID1A基因關(guān)閉的突變（ARID1A基因所編碼的蛋白質(zhì)負(fù)責(zé)DNA捆綁,，即所謂的“染色質(zhì)重塑復(fù)合物”） ,。
染色質(zhì)重塑的變化可更改什么基因被激活或關(guān)閉，因此在腫瘤中喪失ARID1A大概會導(dǎo)致控制癌癥生長基因的不適當(dāng)?shù)谋磉_(dá)（或表達(dá)的喪失）,。 在人類的腫瘤中發(fā)現(xiàn)像ARID1A這樣的具有高頻突變率的基因可為人們提供有關(guān)驅(qū)動腫瘤生長的分子途徑的重要線索,。（生物谷Bioon.com）
生物谷近期特別推薦會議：
2010細(xì)胞治療研究進展與臨床應(yīng)用前沿研討會 www.Cell-therapies.net 2010年9月23日-25日天津召開
第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國際研討會 www.cancerasia.org 2010年10月12日-10月15日上海召開
生物谷推薦英文摘要：
Science DOI: 10.1126/science.1196333
Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma
Sian 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 novel: PPP2R1A encodes a regulatory subunit of serine/threonine phosphatase 2, and ARID1A encodes 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.
1 Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
2 Department of Gynecology and Obstetrics and Oncology, Johns Hopkins Medical Institutes, Baltimore, MD 21231, USA.
3 Department of Pathology, Oncology, Gynecology and Obstetrics, Johns Hopkins Medical Institutes, Baltimore, MD 21231, USA.
4 Department of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
5 Department of Gynecology and Obstetrics, Shimane University, Izumo, Japan.
6 Division of Hematology/Oncology, David Geffen School of Medicine at the University of California, Los Angeles, CA 99095, USA.
