Analysis of K-ras gene mutations in rare pancreatic and ampullary tumours

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 or other non-epithelial tumours of the pancreas. Furthermore, limited data are available regarding the role of K-ras mutations in the pathogenesis of ampullary 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 resection for various rare pancreatic or ampullary neoplasms (number of cases in brackets): ampullary adenoma (1), neuro-endocrine tumour (3), malignant fibrous histiocytoma of the pancreas (1), pancreatic cystadenocarcinoma (1), serous cystadenoma (1), and primary and metastatic adenocarcinoma of the ampulla (5) and pancreas (3), Results K-ras gene mutations at codon 12 were detected in both pancreatic adenocarcinomas and in the metastatic lesion, whereas two ampullary cancers harboured a point mutation at codon 13: GGC-->GGG and GGC-->GGT, None of the other tumours exhibited a K-ras gene mutation at codons 12 or 13. Conclusion Pancreatic tumours other than ductal adenocarcinoma of the pancreas do not harbour mutations of the K-ras oncogene, In addition, ampullary adenocarcinomas may present with codon 13 mutations; however, these mutations were not associated with amino acid substitution. Therefore, K-ras gene mutations seem to be a specific genetic alteration contributing to the pathogenesis of pancreatic ductal adenocarcinoma. Eur J Gastroenterol Hepatol 10:1025-1029 (C) 1998 Lippincott Williams & Wilkins.