BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status.

Background: BRAF is a member of RAF family of serine/threonine kinases and mediates cellular responses to growth signals through the RAS-RAF-MAP kinase pathway. Activating mutations in BRAF have recently been found in about 10% of colorectal cancers, with the vast majority being a V600E hotspot mutation. The aim of the present study was to evaluate the clinical, pathological and molecular phenotype of colorectal tumors with BRAF mutations.

Familial mutations in PMS2 can cause autosomal dominant hereditary nonpolyposis colorectal cancer.

Background & Aims: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder caused by familial mutations in some of the genes responsible for DNA mismatch repair. Mutations in the MLH1, MSH2, and MSH6 genes have been documented in this disorder, but there have been limited and conflicting data about the role of another mismatch repair gene, PMS2. It has recently been suggested that mutations in the PMS2 gene do not cause an autosomal dominant disorder.

The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase.

Purpose: Aberrant DNA methylation occurs in a subset of colorectal cancers and is characterized by regional areas of hypermethylation at CpG islands. The aims of this study were firstly to evaluate the levels of folate intermediates (FIs) in tumors with aberrant DNA methylation and secondly to determine whether these levels are affected by polymorphisms in key genes involved in folate metabolism.

Experimental Design: The concentrations of two major intracellular FIs, 5,10-methylenetetrahydrofolate and tetrahydrofolate (FH4), were measured in 103 surgically resected colorectal cancers.

Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours.

Aim: The aim of this study was to assess the performance of immunohistochemistry using antibodies for MLH1, MSH2, MSH6 and PMS2 mismatch repair gene proteins against microsatellite instability (MSI) testing.

Methods: Tumour samples included in this study were derived from referred patients for screening for hereditary non-polyposis colorectal cancer (HNPCC) and patients who had resections for colorectal cancer that were examined at our institution. MSI was assessed at nine loci (BAT25, BAT26, BAT40, D2S123, D10S197, D17S579, D18S34, D5S346 and D17S250) in all cases.