胰管腺癌(pancreatic ductal adenocarcinoma)是一種無論哪種階段都會致命的癌癥。但是,，有少數(shù)的患者會發(fā)生與囊狀病灶有關(guān)的胰管腺癌,，這種胰管腺癌可以及早檢查，其侵犯性較低,，患者長期存活的比率可高達(dá)百分之50,。
研究人員一直想知道，為什么囊狀胰管腺癌的致死率較低,，囊狀胰管腺癌和一般致死率高的胰臟癌都帶有相同的基因變異,。
現(xiàn)在，F(xiàn)red Hutchinson癌癥研究中心的研究人員解開了這個(gè)謎,。研究人員利用特殊的小鼠模擬兩種人類的胰臟癌,，發(fā)現(xiàn)有常見的基因突變中有一段特殊的序列，使細(xì)胞朝著轉(zhuǎn)移程度較低的路徑發(fā)展,，最終會導(dǎo)致囊狀胰管腺癌,，而沒有這段序列的癌細(xì)胞就會朝著較致命且細(xì)胞轉(zhuǎn)移程度較大的路徑發(fā)展。
這項(xiàng)研究是由Sunil Hingorani所領(lǐng)導(dǎo),，研究結(jié)果將發(fā)表于3月12 日Cancer Cell中,。研究結(jié)果可以解釋為什么胰臟癌細(xì)胞的表現(xiàn)不同。
(資料來源 : 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
