研究人员最新报告称，DNA与蛋白质一同被包裹的方式的某种改变可能会通过造成基因被错误地激活或关闭而促使一种罕见的卵巢癌的发展。
这一发现为不断增加的证据增添了新的内容，即：与将基因组的某部分激活或关闭的化学反应（称作表观遗传控制）有关的蛋白质在人类癌症的发展上起一种关键性的作用。 在本研究中，Sian Jones及其同事在卵巢透明细胞癌中寻找基因突变。透明细胞癌是一种罕见但却特别致命形式的卵巢癌。 在被检验的42个肿瘤中，他们发现有57%的肿瘤含有将ARID1A基因关闭的突变（ARID1A基因所编码的蛋白质负责DNA捆绑，即所谓的“染色质重塑复合物”） 。
染色质重塑的变化可更改什么基因被激活或关闭，因此在肿瘤中丧失ARID1A大概会导致控制癌症生长基因的不适当的表达（或表达的丧失）。 在人类的肿瘤中发现像ARID1A这样的具有高频突变率的基因可为人们提供有关驱动肿瘤生长的分子途径的重要线索。（生物谷Bioon.com）
生物谷近期特别推荐会议：
2010细胞治疗研究进展与临床应用前沿研讨会 www.Cell-therapies.net 2010年9月23日-25日天津召开
第一届肿瘤基础和转化医学国际研讨会 www.cancerasia.org 2010年10月12日-10月15日上海召开
生物谷推荐英文摘要：
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.
