Objective Mutation of the K-ras oncogene is a frequent event in pancreatic
ductal carcinogenesis and it is believed to occur at an early stage in the
development of pancreatic cancer, However, little is known of the role of K
-ras mutations in rare pancreatic epithelial neoplasms, endocrine tumours o
r other non-epithelial tumours of the pancreas. Furthermore, limited data a
re available regarding the role of K-ras mutations in the pathogenesis of a
mpullary tumours.
Design and methods Using single-strand conformation polymorphism (SSCP) and
direct sequencing of polymerase chain reaction (PCR)-amplified fragments,
we analysed codons 12 and 13 for the presence of oncogenic mutations of the
K-ras oncogene. Tissues were obtained from patients undergoing tumour rese
ction for various rare pancreatic or ampullary neoplasms (number of cases i
n brackets): ampullary adenoma (1), neuro-endocrine tumour (3), malignant f
ibrous histiocytoma of the pancreas (1), pancreatic cystadenocarcinoma (1),
serous cystadenoma (1), and primary and metastatic adenocarcinoma of the a
mpulla (5) and pancreas (3),
Results K-ras gene mutations at codon 12 were detected in both pancreatic a
denocarcinomas and in the metastatic lesion, whereas two ampullary cancers
harboured a point mutation at codon 13: GGC-->GGG and GGC-->GGT, None of th
e other tumours exhibited a K-ras gene mutation at codons 12 or 13.
Conclusion Pancreatic tumours other than ductal adenocarcinoma of the pancr
eas do not harbour mutations of the K-ras oncogene, In addition, ampullary
adenocarcinomas may present with codon 13 mutations; however, these mutatio
ns were not associated with amino acid substitution. Therefore, K-ras gene
mutations seem to be a specific genetic alteration contributing to the path
ogenesis of pancreatic ductal adenocarcinoma. Eur J Gastroenterol Hepatol 1
0:1025-1029 (C) 1998 Lippincott Williams & Wilkins.