In melanoma, constitutive activation of the BRAF/MEK/ERK (MAPK) and PI3K/AKT/mTOR (PI3K) signaling pathways plays a pivotal role in cell proliferation, survival and tumorigenesis.
According to the literature, our data provide evidence of the BRAF and RAS roles in thyroid tumorigenesis, supporting an association between BRAF (V600E) mutations and the more aggressive clinical and pathological features of thyroid tumors.
It has been shown that ovarian low-grade serous carcinoma evolves out of a stepwise progression from benign serous cystadenoma to serous borderline tumor (SBT) to micropapillary serous carcinoma (MPSC), and that BRAF activation is a very early somatic event in the tumorigenesis.
Disruption of the Raf/MEK/ERK (MAPK) kinase pathway, either by RAS or BRAF mutation, was detected in approximately 62% of all CC and is therefore one of the most frequent defects in cholangiocellular carcinogenesis.
Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.
Mutations in EGFR, ERBB2, NRAS, and BRAF are early clonal genomic events during carcinogenesis of lung adenocarcinoma, whereas TP53 and cell mobility, gap junction, and metastasis-related genes may be late events associated with subclonal diversification and neoplastic progression.
Here we demonstrate that the expression of an endogenous Braf(D631A) kinase-inactive isoform in mice (corresponding to the human BRAF(D594A) mutation) triggers lung adenocarcinoma in vivo, indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis.
The aim of the present study was to evaluate the methylation status of three cancer-related genes, APC2, p14ARF, and ECAD in colorectal carcinogenesis and their association with the mutational status of BRAF and KRAS among Iranian colorectal cancer patients.
The presence of BRAFV600E and mitogen-activated protein kinase activation in a largely benign tumor supports the necessity for secondary events (e.g., p16 loss) in BRAF-driven oncogenesis.
Although NRAS and BRAF mutation frequency and RAS protein expression are low, BRAF protein expression was intense; probably, NRAS and BRAF mutations are independent events and alternative molecular mechanisms in the primary oral mucosal melanoma tumorigenesis.
In contrast, pathogenic variants classically associated with tumorigenesis in genes like TP53 and BRAF are also present in CD but with low incidence (12.5% and 7%).
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.
Recently, an alternative pathway of tumorigenesis has been identified in the colorectum associated with serrated precursor lesions, variable levels of microsatellite instability (MSI-V), and driven in part by activating mutations in the BRAF proto-oncogene (V599E).
Like the previously reported mutually exclusive relationship between BRAF mutation and other Ras pathway components such as RET/PTC rearrangement, a mutually exclusive relationship also exists between BRAF mutation and RASSF1A methylation in thyroid tumorigenesis.
Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis.
Activating B-Raf mutations arise in 60% to 70% of human melanomas and are thought to play a vital role in tumorigenesis, although how this occurs remains poorly understood.