This survival benefit remained statistically significant in multivariate analyses (P=0.0001) and subgroup analyses of mismatch repair-proficient CRCs (P=0.0001), mismatch repair-deficient CRCs (P=0.031), BRAFV600E-mutant CRCs (P=0.0001), and BRAF wild-type CRCs (P=0.001).
Current clinical guidelines recommend mutation analysis for select codons in KRAS and NRAS exons 2, 3, and 4 and BRAFV600E to guide therapy selection and prognostic stratification in advanced colorectal cancer.
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 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.
Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of survival after CRC, including adjustment for tumor stage, microsatellite instability, and BRAF mutation status.
Mutational status for KRAS, NRAS, and BRAF genes should be performed on all colorectal carcinoma (CRC) specimens in order to guide targeted therapy selection for metastatic disease.
The methylator pathway of colorectal carcinogenesis, characterized by CpG island hypermethylation and BRAF mutations, accounts for ≈25% of colorectal cancers.
Of the 363 patients in the initial cohort, 11(3.0%) harbored oncogenic fusions and were all mismatch repair-deficient colorectal carcinomas with hypermethylated MLH1 and wild-type BRAF and KRAS, comprising 55% (11/20) of this subgroup.
This study was a morphologic reappraisal of 27 colorectal carcinomas arising from TSA (TSA-CRCs) and 53 BRAF-mutated/microsatellite-stable colorectal carcinomas (BRAF-mut/MSS CRCs).
We have used SW48 and LIM1215 human colon cancer cell lines, quadruple wild-type for KRAS, NRAS, BRAF and PI3KCA genes, and their HER2-amplified (LIM1215-HER2 and SW48-HER2) derived cells to perform in vitro and in vivo studies in order to identify novel therapeutic strategies in HER2 gene amplified human colorectal cancer.
Pfizer announced plans to acquire Array BioPharma, maker of a BRAF-MEK inhibitor combination that is currently approved for melanoma and could become a first-in-class treatment for colorectal cancer.
Although BRAF inhibitors have a marked effect on malignant melanoma harboring the BRAF<sup>V600E</sup> mutation, they have a limited effect on patients with CRC with the same BRAF mutation.
The FDA-approved anti-helminthic drug rafoxanide was recently reported to antagonize the oncogenic function of the BRAFV600E mutant protein, commonly found in CRCs, as well as to inhibit the proliferation of skin cancer cells.
The specific features of this <sup>non-V600E</sup> BRAF mutated CRC may be relevant in the exploration of predictive biomarkers for the efficacy of Regorafenib.
Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI).
Detailed morphological evaluation, immunohistochemical analysis of mismatch repair (MMR) proteins, p53 and O<sup>6</sup>-methylguanine DNA methyltransferase (MGMT) expression and molecular analysis for KRAS, NRAS and BRAF gene mutation were performed in the retrieved CRC cases as well as in the detected dysplasia and PPLs of these patients.
On the other hand, p53 mutations which were frequently observed within Indonesian CRCs (76.5%), they were not associated with PD-L1 expression (p=0.1108), as well as KRAS gene (29.6%; p=0.5772) and BRAF gene mutations (5%; p=0.2171).
Right-sided colorectal cancers were more often BRAF mutated and had microsatellite instability, whereas the frequency of RAS mutation was similar between right-sided and left-sided colorectal cancers.