BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05-1.95).
BRAFV600E also predicts poor prognosis in microsatellite stable colorectal cancers and may be a marker of resistance to anti-EGFR therapy in metastatic disease.
BRAF mutations occur at an early stage of colorectal cancer and their presence, 10-20% of colorectal cancer (CRC), is usually associated with inferior prognosis.
BRAF fusions included 3% (14/531) of melanomas; 2% (15/701) of gliomas; 1.0% (3/294) of thyroid cancers; 0.3% (3/1,062) pancreatic carcinomas; 0.2% (8/4,013) nonsmall-cell lung cancers and 0.2% (4/2,154) of colorectal cancers, and were enriched in pilocytic (30%) vs. nonpilocytic gliomas (1%; p < 0.0001), Spitzoid (75%) vs. nonSpitzoid melanomas (1%; p = 0.0001), acinar (67%) vs. nonacinar pancreatic cancers (<1%; p < 0.0001) and papillary (3%) vs. nonpapillary thyroid cancers (0%; p < 0.03).
BRAF mutation was detected in 11 of the 59 tumours analysed (19%) and the rate was significantly higher than the overall BRAF mutation rate of colorectal cancer in patients older than 30 years (p<0.001).
BRAF associated autophagy exploitation: BRAF and autophagy inhibitors synergise to efficiently overcome resistance of BRAF mutant colorectal cancer cells.
BRAF mutation was significantly related with shorter DFS and OS among stage II/III CRC patients receiving adjuvant chemotherapy after curative resection.
BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.
BRAF was mutated in 7.6% (484 of 6353) of colorectal cancer and 9.1% (29 of 317) of SBA samples, but V600E mutations were much less common in SBA, representing only 10.3% (3 of 29) of BRAF-mutated cases.
BRAF inhibition-induced Wnt pathway activation was further validated in preclinical models of <i>BRAF</i><sup>V600E</sup>-mutant colorectal cancer, including cell line xenograft model and a patient-derived xenograft model.
BRAF inhibitor vemurafenib, and subsequent MAPK pathway inhibitors trametinib and SCH772984, significantly increased SPINK1 secretion in V600ECRC cell lines Colo205 and HT-29 with a concomitant decrease in trypsin-1 and -2 secretion.
BRAF mutant microsatellite stable colorectal cancers with the AA genotype most likely arise in TSAs since the A allele does not predispose to methylation in this context.