High frequency of Ki‐ras codon 12 mutations in pancreatic adenocarcinomas

Abstract

The frequency of Ki-ras gene mutations was studied in 100 paraffin-embedded sections obtained from 63 pancreatic adenocarcinomas by in vitro amplification of target sequences via polymerase chain reaction (PCR) and selective oligonucleotide hybridization. Forty-seven (75%) of the tumors contained a Ki-ras mutation at codon 12. No predominant amino acid substitution or nucleotide transition at this codon was observed. Two carcinomas exhibited 2 distinct Ki-ras mutations. No particular correlation could be established between the incidence of Ki-ras mutation and clinical parameters (sex, age, survival), tumor grade or tumor stage.

Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma

“…[3][4][5][6][7][8] This mutant mRNA is a likely target for Rz-mediated gene modulation, because the activated ras oncoproteins are thought to alter the cellular signal transduction pathways and to affect the neoplastic growth of pancreatic cancers. The anti-Kras hammerhead Rz we designed efficiently cleaved the target mutant K-ras RNA in the cell-free system.…”

The K-ras mutation pattern in pancreatic ductal adenocarcinoma usually is identical to that in associated normal, hyperplastic, and metaplastic ductal epithelium

“…The codon 12 of this gene is affected in 80-100% of the cases. 3,4,20 Mutated K-ras also has been found in ductal lesions such as mucinous cell hypertrophy and ductal papillary hyperplasia 16 ; therefore these lesions have been regarded as precursor lesions of carcinoma. 9 However, this assumption is based on rather contradictory results, with K-ras mutation rates in ductal lesions ranging from 0-94%.…”

“…2 The highest incidence of K-ras mutation has been found in ductal adenocarcinoma of the pancreas, in which it ranges from 70-100%. [3][4][5] Because K-ras mutations have been found in very small incidental carcinomas, which were diagnosed only at autopsy, 6 as well as in intraductal portions of ductal carcinomas, it is considered an initial event in carcinoma development. This may make it a good tool for detecting pancreatic carcinomas at an early stage.…”

Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial

“…Therefore, reovirus represents a potentially useful treatment for a wide variety of solid and haematological tumours including pancreatic, colorectal, thyroid and lung cancers and acute myelogenous leukaemia. [9][10][11][12][13] RT3D is currently undergoing extensive evaluation in phase I and II clinical trials, either as a single agent or in combination with radiotherapy or cytotoxic chemotherapy.…”