In this study, 40 wild type KRAS and BRAFcolorectal tumors were analyzed to elucidate whether PML-RARa bcr1 fusion gene may play a role in colorectal carcinogenesis.
To verify the technical characteristics of the microarray system for the correct identification of the KRAS mutational status at the two hotspot codons 12 and 13 and of the BRAF(V600E) mutation in colorectal tumor, we selected 75 samples previously characterized by conventional and CO-amplification at Lower Denaturation temperature-PCR (COLD-PCR) followed by High Resolution Melting analysis and direct sequencing.
Vemurafenib doesn't shrink BRAF-mutated colorectal tumors, but a regimen that also includes irinotecan and cetuximab improves vemurafenib's effectiveness, more than doubling progression-free survival in patients with metastatic tumors.
Recently, a V599E hotspot mutation within the BRAF gene was reported in a high percentage of colorectal tumors and significantly associated to defective mismatch repair (MMR).
TRAP1 is involved in BRAF regulation and downstream attenuation of ERK phosphorylation and cell-cycle progression: a novel target for BRAF-mutated colorectal tumors.
This article reviews the current knowledge on the use and implications of BRAF mutational status in colorectal tumors, in order to define its present role in the clinical practice.
The studies were divided into five groups: (1) distribution of KRAS/BRAF mutations in distal and proximal colorectal cancer, the summary OR value was 1.24 versus 4.03, (2) distribution of KRAS/BRAF mutations in CIMP-low/Neg and CIMP-high (CIMP-H) tumors, the summary OR value was 0.77 versus 10.49, (3) distribution of KRAS/BRAF mutations in MSI-low (MSI-L)/microsatellite stable (MSS) and MSI-high (MSI-H) tumors, the summary OR value was 0.51 versus 9.60, (4) proportion of CIMP-H/MSI-H tumors among distal and proximal colorectal tumors, the summary OR value was 3.66 versus 6.54, and (5) proportion of CIMP-H tumors among MSI-L/MSS and MSI-H tumors, the summary OR value was 5.87.
A previous analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant BRAF and both events proved to cooperate in tumor cell survival.
Significantly, systemically administered rIGFBP7 blocks the growth of colorectal tumors containing an activating RAS or BRAF mutation in mouse xenografts.
Different effects of point mutations within the B-Raf glycine-rich loop in colorectal tumors on mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase and nuclear factor kappaB pathway and cellular transformation.
Secondly, considering the alternative possibility, we identified genes whose DNA hypermethylation was closely linked to BRAF(V600E) and CIMP in 235 primary colorectal tumors.
We investigated the clinical and molecular features of the MSH6 variants, such as the family cancer history, pathological findings, immunohistochemistry, methylation status of the MLH1 promoter and BRAF mutation in the colorectal tumor.