The aim of the present study was to further verify these observations by including BRAF gene analysis and by investigating a larger series of cases subdivided into Dukes' stages A to D to reconstruct some form of chronological modulation for events during CRC progression.
BRAF mutation testing has therefore been proposed as a means to more definitively identify and exclude sporadic MSI-H CRC cases from germline MMR gene testing.
CpG island methylator phenotype (CIMP) is a phenotype of colorectal cancer with extensive promoter methylation, and associated with high degree of microsatellite instability (MSI-H) and BRAF mutations.
The CpG island methylator phenotype (CIMP) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, associated with microsatellite instability-high (MSI-high) and BRAF mutations.
We analyzed MSI using the 6 microsatellite markers and a frameshift mutation in the BRAF gene and in poly(A)9 within the Chk1 gene in 51 sporadic colorectal cancer and 14 HNPCC specimens.
Our finding of a strong association between BRAF mutations and serrated histology in hyperplastic ACF supports the idea that these lesions are an early, sentinel, or a potentially initiating step on the serrated pathway to colorectal carcinoma.
Our observations suggest that Raf and MEK inhibitors may be effective for the treatment of B-RAF mutation-positive colorectal carcinomas as well as melanomas.
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.
We demonstrated that KRAS and BRAF are alternative events in Tis and T1 MSS CRC and, KRAS rather than BRAF mutations, contributed to the progression of MSS CRC.
Site-specific activation was apparent in the cell signaling mitogen-activated protein kinase oncogenes (KRAS in lung, HRAS in oral cancers and BRAF in esophageal and colorectal cancers).
The reference tumor group contained 28 HNPCC with proven germ-line mutations or positive Amsterdam I criteria (median age, 37 years) and loss of MLH1 expression, 14 sporadic MSI-H CRC tumors with loss of MLH1 expression and BRAFV600E mutation (median age, 80.5 years), and 16 sporadic MSS CRC (median age, 76.5 years).
The BRAF, KRAS and PI3KCA genes code 3 partners of this network and have been found to be activated by mutation in colorectal cancer; these mutations lead to unrestricted cell growth.
That pattern of increased sensitivity to phenothiazines based on the presence of codon 600 BRAF mutation may be unique to melanomas, as we do not observe it in a panel of colorectal cancers.