We reproducibly associate higher expression of the ligand-receptor axis of TFF2 and CXCR4 with BRAFV600E-mutant colon cancer (P = 3.0 × 10(-3) and 0.077, respectively for TCGA; P = 3.0 × 10(-8) and 5.1 × 10(-7) for CIT).
We investigated the role of BRAF activating mutation (BRAF-V600E) in colorectal tumourigenesis by studying the effects of forced expression of BRAF-V600E in the 'normal' colon epithelial NCM460 cell line and by targeting endogenous BRAF-V600E in MSI-High (MSI-H) colon cancer cell lines.
We have tested a battery of melanoma and colon carcinoma cell lines that carry mutations in BRAF, NRAS and KRAS genes and have observed that those with NRAS and KRAS mutations are more sensitive to killing by IPA3.
We determined the effects on clinical outcome of the BRAF mutation, microsatellite instability (MSI) and KRAS mutations in stage II and stage III colon carcinoma.
We conclude that the BRAFV600E mutation in microsatellite-stable colon cancer is associated with a significantly poorer survival in stages 2 to 4 colon cancer but has no effect on the excellent prognosis of microsatellite-unstable tumors.
To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab.
To date, identification of HER2 expression in gastric adenocarcinoma and KRAS, NRAS and BRAF mutations in colon cancer have proved essential for treatment decisions.
This study shows that BRAF mutations profiled from stage II and III colon cancer tumors were associated with poor SAR and validates and explains, at least in part, previous observations associating it with poor OS.
These results indicate that molecular analysis for BRAF may be a useful biomarker for identifying patients with right-sided colon cancer with poor outcome who may benefit from a more individualized course of therapy.
These findings illustrate the utility of non-invasive PET imaging measures of glutamine uptake to selectively predict response to BRAF-targeted therapy in colon cancer and may suggest further opportunities to inform colon cancer clinical trials using targeted therapies against MAPK activation.
These data suggest that the BRAFV600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer.
There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer.
The subgroup of colon cancer (CRC) characterized by mutation in the BRAF gene and high mutation rate in the genomic DNA sequence, known as the microsatellite instability (MSI) phenotype, accounts for roughly 10% of the patients and derives from polyps with a serrated morphology.
The mutational status of KRAS and BRAF(V600E) oncogenes combined with analysis of the DNA mismatch repair system with/without the CpG island methylator phenotype (CIMP) has been shown to identify colon cancer subtypes with distinct clinical features and prognoses.
The kinetics of ctDNA derived from each cancer type were monitored targeting BRAFV600R (melanoma) and KRAS G13D (colon cancer), specifically reflected the status of the patient's tumours.
The demonstration that BRAF is a human oncogene mutated at high frequency in melanoma, thyroid and colon cancer has provided a pathophysiological context, whilst the description of potent and highly selective inhibitors of BRAF or MEK has allowed a more informed and rational intervention in both normal and tumour cells.
The CpG island methylator phenotype (CIMP-high, CIMP1) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer.
The clinical studies in the manuscript by Al-Marrawi et al. describe the rational combination of signaling inhibitors in a colon cancer patient whose tumor cells express a mutant active B-RAFV600E protein that signals into the MEK1/2-ERK1/2 pathway downstream of K-RAS; this is a particularly aggressive form of colon cancer for which few rational therapeutic interventions have been available until recent times.