Clinicopathologic and Molecular Features of Pancreatic Adenocarcinoma Associated with Peutz-Jeghers Syndrome

Abstract

Pancreatic cancer is increasingly prevalent and almost uniformly fatal. Studies of the molecular genetics of sporadic and hereditary cases of pancreatic cancer as well as the molecular biology of pancreatic development may advance our understanding of the mechanism underlying pathogenesis of this malignancy. Based on a case of pancreatic adenocarcinoma in a patient with Peutz-Jeghers syndrome (PJS), the clinicopathologic features and molecular genetics of pancreatic tumors associated with this hereditary cancer syndrome are reviewed. Particular emphasis is placed on the developmental roles and biochemical functions of STK11/LKB1, the gene mainly responsible for PJS. Modeling pancreatic cancer in animal models such as the mouse and zebrafish will further our understanding of the pathogenesis of this important disease, and the studies derived from these model organisms can be potentially applied for developing novel preventive and therapeutic strategies.

LKB1; linking cell structure and tumor suppression

“…A markedly increased incidence of carcinomas of the gastrointestinal tract including stomach, small bowel, colon and pancreatic cancer, as well as breast, ovary, uterus, cervix, lung and testis cancer has been observed through longitudinal studies of affected kindreds (Giardiello et al, 1987(Giardiello et al, , 2000Spigelman et al, 1989;Gruber et al, 1998;Lim et al, 2004;Hearle et al, 2006). In addition, rare tumors have been associated with PJS including those of a reproductive origin-including testicular and ovarian sex cord tumors, Sertoli cell tumors and adenoma malignum of the cervix-as well as non-adenocarcinoma pancreatic tumors, including pancreatic intraductal papillary mucinous neoplasia and serous cystadenomas (Podczaski et al, 1991;Young et al, 1995;Tomlinson and Houlston, 1997;Su et al, 1999;Sato et al, 2001;Yee et al, 2003).…”

Analysis Of STK11/LKB1 Gene Using Bioinformatics Tools

“…Strong expression of STK11/LKB1 in human fetal small intestine and stomach suggests that STK11/LKB1 has a regulatory function in the development and maintenance of the embryonic gastrointestinal tract (11).…”

Werner syndrome as a hereditary risk factor for exocrine pancreatic cancer

“…10 We propose that WS is a novel hereditary pancreatic cancer predisposition syndrome by causing a DNA repair defect and chromosomal instability in pancreatic epithelia (Table 2, Fig. 3).…”

“…10,11 Werner syndrome (WS) is a disorder of accelerated aging with onset during adolescence that is inherited in an autosomal recessive fashion. It is caused by loss-of-function mutations of the WRN gene that encodes a DNA helicase of the RecQ family possessing an exonuclease domain.…”