摘要Pancreatic carcinoma is the most common pancreatic neoplasm characterized by latentmorbidit, poor prognosis, high mortality rate and limited choice of treatment. Quite a lot studies focused on its pathogenesis, and showed molecular genetic alterations, which derived of genetic and environmental factors and played an important role in tumorigenesis. Recently, more and more findings laid particular emphasis on the changes of gene molecule and some were confirmed in vitro and in vivo. In this paper, we made a review and summarized the arked molecular changes and signalings of the four pathways to understand their functions in Pancreatic carcinoma. The most important changes concentrate on K-RAS, p16 INK4α, P53 and SMAD4 gene, secondly, the changes of pl4ARF, TGF-β, LKB1 /STK11, BRCA2 and growth factor Hedgehog and Notch path way and Telomere also play a important role in pancreatic carcinoma. The vast majority (83%) of pancreatic carcinomas had a distinctive genetic fingerprint, comprising activation of the K-ras oncogene and inactivation of the p 16 gene, generally also accompanied by alterations in the p53 gene (in 76 % of the tumors). The activation of K-ras appears nearly to be a prerequisite for the development of pancreatic carcinoma. Also, the binary alteration of K-ras and p16 is an extremely uncommon combination among other human tumor types. This particular genetic imprint of pancreatic carcinomas could have diagnostic utility in the evaluation of patients with metastatic adenocarcinoma of unknown primary origin. The evaluation of genetic alterations as they naturally occur in humantumors allows the formulation of hypotheses concerning the biological processes that involve human tumongenesis. A central tenet of tumori genesis, that positive selection is exerted upon those tumor cells that alterrate-limiting regulatory pathways, implies that mutation of one gene abrogates the need for inactivation of another gene in the same tumor suppressive pathway. It follows, therefore, from the genetic profile of pancreatic carcinoma that K-ras, p53, pi6, DPC4,and BRCA2 each belong to a distinct tumor-suppressive pathway. The concept of distinct tumorsuppressive pathways, however, should not exclude the possibility of cooperative interactions between the pathways. In this series, for example, DPC4gene inactivation was limited to tumors with genetic inactivation of the p16 gene. The involvement of the p13, p16, and DPC4 pathways in pancreatic carcinoma is likely to be even greater than suggested by our current mutational analysis. For example, we have not yet addressed the mutational status of the RBi gene, which participates in the same pathway as p16 and has been reported to be mutated in about 7% of pancreaticearcinomas. Also, methylation abnormalities that might abrogate the expression of the p16 protein have yet to be evaluated in our collection of pancreatic carcinomas. The identification of such additional genetic targets would improve the description of the genetic profile of pancreatic carcinoma and thus enhance our understanding of the tumor-suppressive pathways that are involved in the development of this tumor type.