Adenocarcinomas from the left side of the colorectum showed a significant association between C-KI-RAS activation and tumour progression, including the presence of distant organ metastasis at the time of surgery (P = 0.0039), and during patient follow-up (P = 0.00027), whereas those from the right of the colorectum did not (P = 0.4 and P = 0.5, respectively).
Topographic genotyping with subsequent polymerase chain reaction (PCR) and sequence analysis of K-ras-2 showed mutations in significantly fewer cases of PC (9%, 2 of 22 cases) than in AdC (36%, 35 of 97 cases) or SqC (0%, 0 of 42 cases) (P < .001).
Since little is known of its role in pancreatic cancers, we investigated changes in telomerase activity in human pancreatic duct adenocarcinomas and compared the frequency of increased telomerase activity with the presence of K-ras gene mutations.
Point mutations in exon 1 of KRAS and in exon 7 of TP53 were evident by polymerase chain reaction (PCR)-DNA sequencing in the RAL cell line, whereas no alterations were present in the HRAS and RB genes.
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.
Meanwhile, 11 (58 per cent) serrated adenomas and six (60 per cent) adenocarcinomas in/with serrated adenomas had Ki-ras gene mutations, as also did 9 of 23 (39 per cent) hyperplastic nodules, 3 of 4 (75 per cent) hyperplastic polyps, and 12 of 29 (41 per cent) tubular adenomas.
The prevalence of mutations in K-ras gene was 1/8 (13%) in mucinous, 7/29 (24%) in serous, 1/3 (33%) in endometrioid and 2/8 (25%) in clear-cell adenocarcinomas and in H-ras gene 1/8 (13%) in mucinous and 2/29 (7%) in serous adenocarcinomas.
The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas.
Our data demonstrates that the K-ras gene mutations are mainly affected (47%) in the malignant cells of the peritoneal washings or ascites of women with ovarian adenocarcinomas and may have value for the early diagnosis and monitoring of these neoplasms.
To determine if the incidence of H- and K-ras gene mutations in these rat tumors is similar to that in human endometrial cancers, we isolated DNA samples from 2 atypical hyperplasias, 5 simple or complex hyperplasia without atypia, 9 adenocarcinomas and 7 histologically normal tissues, amplified exons 1 and 2 of the H- and K-ras genes by PCR and hybridized the products with allele specific oligonucleotide probes.
The K-ras gene was mutated in only 2 samples (8%): a GGC-to-ATC mutation at codon 13 in an adenocarcinoma and a GGC-to-GTC transversion mutation at codon 13 in a mucoepidermoid carcinoma.
In the other tumors, more complex aberrations were visualized, including two inversions in 12q with a common breakpoint between MDM2 and D12S332 in a pleomorphic adenoma, amplification of MDM2 and CDK4 in ring chromosomes from a malignant fibrous histiocytoma, and amplification of KRAS2 together with other unbalanced rearrangements in two pancreatic adenocarcinomas.
The K-Ras oncogene, mutated in 46-50% of CRC tumors, serves as one molecular marker by which stool samples may be evaluated for early detection of adenocarcinomas.
Mutations of the K-ras gene were detected in 6 of 100 (6%) and 15 of 93 (16.1%) adenocarcinoma cases with the GSTM1(+) and GSTM1(-) genotypes, respectively, and the difference was statistically significant.
Activated point mutations of the K-ras gene are one of the most common genetic alterations found in human malignancies, including lung cancer, and are largely limited to adenocarcinomas.