Colorectal cancer is one of the most common cancers in industrialized countries. Approximately 10 to 15% of cases are caused by inherited genetic abnormalities that cause syndromes such as familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC).
HNPCC accounts for 5 to 10% of all colorectal cancers. Patients with HNPCC have an increased risk of developing colon and endometrial cancer at an early age, and therefore they are subjected to intense surveillance protocols. Consequently, early diagnosis of HNPP is crucial for the proper monitoring and treatment of these patients and their families.
Genetically, 50% of HNPCC cases are caused by mutations in genes for DNA mismatch repair (MMR). Loss of these MMR genes function is reflected in a phenomenon called microsatellite instability (MSI)- sequences of repeated DNA that are altered in these patients-. In patients with tumors with high MSI (MSI-H) or loss of function of MMR genes, the diagnosis of HNPCC has to be confirmed by sequencing MMR genes.
On the other hand, sporadic (non-familial) colorectal cancer patients can show MSI-H. Therefore, differential diagnosis is important in order to rule out HNPCC syndrome in these sporadic cancer patients.
BRAF gene is involved in cell signaling and proliferation, and abnormal activation can cause cancer. One particular mutation, V600E BRAF, appears in 90% of patients with activating mutations of the gene. Moreover, BRAF-V600E mutation was detected in 40% of cases of sporadic colorectal tumors with MSI-H but not in HNPCC tumors or tumors with loss of MMR gene expression (see article).
Therefore, the presence of the BRAF-V600E mutation in colorectal tumors with MSI-H reflects wit high probability that the cancer is sporadic rather than HNPCC.
ColoBRAF™ simplifies genetic testing for HNPCC by reducing the need for sequencing MMR genes.
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