@article{15a0b107a83b4e3fa6eb1e317871b631,
title = "KrasG12D and Smad4/Dpc4 Haploinsufficiency Cooperate to Induce Mucinous Cystic Neoplasms and Invasive Adenocarcinoma of the Pancreas",
abstract = "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.",
keywords = "CELLCYCLE",
author = "Kamel Izeradjene and Chelsea Combs and Melissa Best and Aarthi Gopinathan and Amary Wagner and Grady, {William M.} and Deng, {Chu Xia} and Hruban, {Ralph H.} and Adsay, {N. Volkan} and Tuveson, {David A.} and Hingorani, {Sunil R.}",
note = "Funding Information: We thank Bethann Pflugeisen for outstanding assistance with figure preparation; Julie Randolph-Habener, Kim Adolphson, and the FHCRC Experimental Histopathology laboratory, as well as Barbara Pruetz, for expert assistance with immunohistochemistry; and Philamer Calses for excellent technical assistance. We are also grateful to Dr. Testuo Sudo for the kind gift of anti-Hes1 antibody. We apologize to colleagues for our inability to cite many primary references due to space constraints. Supported in part by NCI P50 CA62924 (R.H.H.); NIH R01 CA101973 and NIH U01 CA084291 (D.A.T.); and NCI P30 CA15704, AACR-PanCAN Career Development Award, and the Canary Foundation (S.R.H.). ",
year = "2007",
month = mar,
day = "13",
doi = "10.1016/j.ccr.2007.01.017",
language = "English (US)",
volume = "11",
pages = "229--243",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}