| Summary: | <p>Abstract</p> <p>Background</p> <p>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 <it>BRAF </it>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 <it>BRAF </it>mutations.</p> <p>Results</p> <p>Mutations in <it>BRAF </it>were identified in 8% (23/275) of colorectal cancers. They were 5–10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (<it>P </it>< 0.002 for each). Tumors with <it>BRAF </it>mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (<it>P </it>< 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with <it>BRAF </it>mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. Mutations in <it>BRAF </it>were mutually exclusive with mutations in <it>KRAS </it>but showed no clear association with the presence of <it>TP53 </it>mutation.</p> <p>Conclusion</p> <p><it>BRAF </it>mutation identifies a colorectal cancer subgroup with distinctive phenotypic properties independent of microsatellite instability status and thus could be a valuable marker for studies into the clinical properties of these tumors.</p>
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