In this prospective study of older women, cigarette smoking was associated with the MSI-high, CIMP-positive, and BRAF mutation-positive colorectal cancer subtypes, which indicates that epigenetic modification may be functionally involved in smoking-related colorectal carcinogenesis.
DNA extraction was attempted on 11 search-retrieved paired cases of histological resections or excisions of CRC and their corresponding cytological samples (representing metastases) and tested for KRAS mutations in exon 2 and 3, as well as BRAF exon 15 mutations by Sanger sequencing.
There were also tendencies toward associations of Fn-high with the BRAFV600E mutation (P = 0.047) and active Crohn-like lymphoid reactions (P = 0.052) in MSI-H CRCs.
Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017).
We investigated the associations between v-Raf murine sarcoma viral oncogene homolog B1 (<i>BRAF</i><sup>V600E</sup>, henceforth <i>BRAF</i>) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog <i>(</i><i>KRAS</i>) mutations and colorectal cancer (CRC) prognosis, using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE39582) datasets.
The SIM-AIMS assay could also detect WT and V600EBRAF in CRC specimens, but the measured levels of both targets were lower than those determined by MRM assay.
Sporadic colorectal cancers with a high degree of microsatellite instability are a clinically distinct subgroup with a high incidence of BRAF mutation and are widely considered to develop from serrated polyps.
Ahronian and colleagues show that in BRAF-mutant colorectal cancer, resistance involves reactivation of RAS/RAF/MEK/ERK signaling and may be overcome by newly emerging ERK inhibitors.
Characterisation of BRAF(wt) MSI CRC revealed hot-spot mutations in well-known oncogenic drivers, including KRAS (38.7%), PIK3CA (36.5%), and ERBB2 (15.0%).
The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations.
In colorectal cancer (CRC), the molecular characterization of RAS and BRAF mutation status for prognostic and predictive purposes is commonly performed by different validated methods.
In this study, we explored the effect of combined use of dabrafenib, a BRAF inhibitor, and cetuximab, an EGFR inhibitor, on BRAF(V600E)-mutant CRC stem cells and its possible mechanisms.
<b/> BRAF mutations in colorectal cancer portend a poor prognosis, with first-line treatment often involving triplet or quadruplet chemotherapy, and single-agent targeted therapy with BRAF inhibitors failing to demonstrate clinical activity.