Clinical implications of BRAF mutation test in colorectal cancer

Knowledge about the clinical significance of V-Raf Murine Sarcoma Viral Oncogene Homolog B1 [BRAF] mutations in colorectal cancer [CRC] is growing. BRAF encodes a protein kinase involved with intracellular signaling and cell division. The gene product is a downstream effector of Kirsten Ras [KRAS] within the RAS/RAF/MAPK cellular signaling pathway. Evidence suggests that BRAF mutations, like KRAS mutations, result in uncontrolled, non-growth factor-dependent cellular proliferation. Similar to the rationale that KRAS mutation precludes effective treatment with anti-EGFR drugs. Recently, BRAF mutation testing has been introduced into routine clinical laboratories because its significance has become clearer in terms of effect on pathogenesis of CRC, utility in differentiating sporadic CRC from Lynch syndrome [LS], prognosis, and potential for predicting patient outcome in response to targeted drug therapy. In this review we describe the impact of BRAF mutations for these aspects

CpG island methylator phenotype [CIMP] in colorectal cancer

It is clear that colorectal cancer [CRC] develops through multiple genetic and epigenetic pathways. These pathways may be determined on the basis of three molecular features: [i] mutations in DNA mismatch repair genes, leading to a DNA microsatellite instability [MSI] phenotype, [ii] mutations in APC and other genes that activate Wnt pathway, characterized by chromosomal instability [CIN] phenotype, and [iii] global genome hypermethylation, resulting in switch off of tumor suppressor genes, indicated as CpG island methylator phenotype [CIMP]. Each of these pathways is characterized by specific pathological features, mechanisms of carcinogenesis and process of tumor development. The molecular aspects of these pathways have been used clinically in the diagnosis, screening and management of patients with colorectal cancer. In this review we especially describe various aspects of CIMP, one of the important and rather recently discovered pathways that lead to colorectal cancer