Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the other twin harbored a different mutation.
The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC).
We investigated mutations of the APC, beta-catenin, and K-ras genes, and microsatellite instability (MSI) status in 35 adenomas and 47 flat dysplasias without adenocarcinoma, 35 adenomas/dysplasias associated with adenocarcinomas, and 39 adenocarcinomas (20 diffuse type and 19 intestinal type).
Ki-ras gene mutations were found more frequently in LST (6/28 tumors) and polypoid adenomas (6/23 tumors) than in IIa-type adenomas (2/22 tumors), although this difference was not statistically significant.
These findings suggest that BRAF mutations are early and a critical event in the serrated adenomas, and most serrated adenomas in both sides of colon may progress from microvesicular hyperplastic polyps via BRAF mutations, and some left-sided serrated adenomas develop via KRAS mutations.
On stratification of cases, MGMT activity was found to be considerably greater in the normal mucosa of cases with large adenomas (p = 0.003) and slightly higher in cases with a GC-->AT transition mutation in the K-ras gene (p = 0.03).
Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in sporadic colorectal adenomas with demographic and clinicopathologic characteristics.
Overall, our data suggest that an alteration in the c-Ki-ras gene results in a switch to a suppressive type of immune response, determining an impairment of immune cell activation at both antigen- presenting-cell and T-cell levels. c-Ki-ras gene mutations, p53 deletions, and Bc12 expression, on the other hand, can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma.
KRAS2 mutations were found in 43% of the goblet cell serrated polyp (GCSP) category, 13% of MVSPs, 7% of SPAPs, and 24% of SAs; in 26% of large traditional adenoma (lTAs) compared with small traditional adenomas (sTAs) (0/30; P<0.005) and in 37.3% of traditional carcinomas (TCa).
KRAS mutation in G-to-A transitions at codons 12 and 13 was detected in a significantly higher percentage of flat-type adenomas (26%) than in protruded-type adenomas (9%).
The findings demonstrated the positive association of the BRAF mutation, V600E, with sessile serrated adenomas and KRAS mutations with tubular adenomas (p < 0.05).
These findings suggest that, following APC loss, CtBP1 contributes to adenoma initiation as a first step, whereas KRAS activation and beta-catenin nuclear localization promote adenoma progression to carcinomas as a second step.
Alterations of APC, KRAS and TP53 were observed in a higher percentage of adenocarcinomas compared to adenomas (P<0.05) indicating that the alterations accumulated with malignancy.
Increased cytoplasmic and/or nuclear beta-catenin staining was seen in 94% and 80% of the adenomas. beta-Catenin nuclear staining was strongly associated with MYC levels (p value 0.03) but not with KRAS mutations.Copy number aberrations were rare.
As K-ras mutations are very rare in these adenomas, Runx3+/- mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation.