Our data document (a) the absence of BRAF mutations in cervical and endometrial cancer, despite the mutation status of KRAS, (b) suggest that KRAS mutations reflect an early event in endometrial carcinogenesis and (c) imply that BRAF activation is involving alternative pathways in these two types of cancer.
These results have important implications concerning the mechanism of oncogenesis in melanoma as well as in the response of the tumor to anticancer drugs targeting BRAF or c-kit.
Thus, BRAF mutations most likely participate in de novo colorectal carcinogenesis, K-ras mutations in the adenoma-carcinoma sequence of colorectal carcinogenesis, and RASSF1A promoter methylation in both cascades.
These results show that RASSF2A methylation is a frequent event in colorectal tumorigenesis and positively correlates with K-ras/BRAF mutation in microsatellite-stable or distal CRC.
This study aimed to evaluate the status of BRAF together with K-ras, p53 and mismatch-repair deficiency to clarify their association with tumorigenesis of colorectal MC.
These data suggest that BRAF is a less frequent mechanism of tumorigenesis in a background of CLT and that BRAF mutation is not present in the atypical follicular epithelium of CLT.
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.
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.
The panel of cell lines we have studied displayed activation of several oncogenes (BRAF, RAS, RET/PTC) and inactivation of tumor suppressor genes (TP53) known to be important for thyroid carcinogenesis.
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.
The B-Raf(V600E) mutant, found in 65% of human melanomas, drives constitutive activation of the extracellular signal-regulated kinase (ERK) pathway and is implicated in tumorigenesis.
The data from the current study suggest that, as shown previously in colon cancer, aberrant methylation of the hMLH1 gene may play a role in BRAF mutation-promoted 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.
In particular, evidence for oncogene-induced melanocyte senescence as natural means to prevent tumorigenesis has been obtained in nevi with mutated B-Raf(V600E).