新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » Cell报道 » Cancer Cell: 可治疗和不能治疗的胰脏癌之基因路径

Cancer Cell: 可治疗和不能治疗的胰脏癌之基因路径

来源:华文生技网 2007-03-21 10:59

    胰管腺癌(pancreatic ductal adenocarcinoma)是一种无论哪种阶段都会致命的癌症。但是,有少数的患者会发生与囊状病灶有关的胰管腺癌,这种胰管腺癌可以及早检查,其侵犯性较低,患者长期存活的比率可高达百分之50。

    研究人员一直想知道,为什么囊状胰管腺癌的致死率较低,囊状胰管腺癌和一般致死率高的胰脏癌都带有相同的基因变异。

    现在,Fred Hutchinson癌症研究中心的研究人员解开了这个谜。研究人员利用特殊的小鼠模拟两种人类的胰脏癌,发现有常见的基因突变中有一段特殊的序列,使细胞朝着转移程度较低的路径发展,最终会导致囊状胰管腺癌,而没有这段序列的癌细胞就会朝着较致命且细胞转移程度较大的路径发展。

    这项研究是由Sunil Hingorani所领导,研究结果将发表于3月12 日Cancer Cell中。研究结果可以解释为什么胰脏癌细胞的表现不同。

     (资料来源 : Bio.com)

部分英文原文:

Volume 11, Issue 3 , 13 March 2007, Pages 229-243

KrasG12D and Smad4/Dpc4 Haploinsufficiency Cooperate to Induce Mucinous Cystic Neoplasms and Invasive Adenocarcinoma of the Pancreas

Kamel Izeradjene1, 3, Chelsea Combs4, Melissa Best1, Aarthi Gopinathan4, Amary Wagner4, William M. Grady1, 3, Chu-Xia Deng5, Ralph H. Hruban6, N. Volkan Adsay7, David A. Tuveson4 and Sunil R. Hingorani1, 2, 3,

1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
2Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
3University of Washington School of Medicine, Seattle, WA 98109, USA
4Abramson Family Cancer Research Institute and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
5Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
6Departments of Pathology and Oncology, Sol Goldman Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
7Department of Pathology, Harper Hospital and Wayne State University School of Medicine, Detroit, MI 48201, USA

Received 18 August 2006;  revised 1 November 2006;  accepted 19 January 2007.  Published: March 12, 2007.  Available online 12 March 2007.

Summary

Oncogenic Kras initiates pancreatic tumorigenesis, while subsequent genetic events shape the resultant disease. We show here that concomitant expression of KrasG12D and haploinsufficiency of the Smad4/Dpc4 tumor suppressor gene engenders a distinct class of pancreatic tumors, mucinous cystic neoplasms (MCNs), which culminate in invasive ductal adenocarcinomas. Disease evolves along a progression scheme analogous to, but distinct from, the classical PanIN-to-ductal adenocarcinoma sequence, and also portends a markedly different prognosis. Progression of MCNs is accompanied by LOH of Dpc4 and mutation of either p53 or p16. Thus, these distinct phenotypic routes to invasive adenocarcinoma nevertheless share the same overall mutational spectra. Our findings suggest that the sequence, as well as the context, in which these critical mutations are acquired helps determine the ensuing pathology.

Author Keywords: CELLCYCLE

 

相关报道:

胰脏癌中异常表现的microRNA有助于新诊断方法的研发

从海洋生物身上找到抗癌化合物

可能是单一基因启动了癌细胞的转变

胰腺癌的基因诊断研究现状

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库