BRAF mutations represent an alternative molecular pathway in the early tumorigenesis of a subset of KIT/PDGFRA wild-type GISTs and are per se not associated with a high risk of malignancy.
BRAF(V600E) mutation is an early event in thyroid carcinogenesis, and is associated with distinctive morphology and aggressive features even in papillary thyroid microcarcinomas.
A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.
A previous study identified a novel gene, monopolar spindle protein kinase 1 (Mps1), a downstream target of BRAF<sup>V600E</sup> only, rather than of wild-type BRAF as well, which contributes to tumorigenesis in melanoma.
Aberrant signaling of the Ras-Raf-MEK-ERK (MAP kinase) pathway driven by the mutant kinase BRAF(V600E), as a result of the BRAF(T1799A) mutation, plays a fundamental role in thyroid tumorigenesis.
Abnormal/high DDR type of 53BP1 expression might be associated with GIN and papillary/trabecular morphology at an early stage of PTC carcinogenesis through BRAF(V) (600E) mutation.
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.
Activating BRAF point mutations, RAS aberrations, and RET rearrangements are mutually exclusive events in the oncogenesis of papillary thyroid carcinoma, and RET rearrangements have been previously described in dominant nodules of HT.
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.
Activating mutations of KRAS and BRAF genes are genetic events in tumorigenesis and these mutations are implicated as predictive factors in determining response, in particular to anti-EGFR drugs, and additional data suggest that other EGFR downstream pathways such as PI3K/PTEN/Akt or JAK/STAT are also important when considering mechanisms of EGFR antibody resistance.
Although BRAF mutation has been reported in a variety of other human cancers, it is a rare event in the carcinogenesis and progression/development of gastric cancer.
Although a high prevalence of BRAF mutation has been suggested as an important event in thyroid tumorigenesis, little is known about the expression pattern of B-Raf in the thyroid.
Although further extensive screenings are awaited in HCC patients among different populations, our findings clearly indicated that mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population.