BRAF mutation (tumour DNA)

BRAF V600E mutation in around 10 % of bowel cancers. Is looked at in bowel cancer diagnostics.

What the BRAF gene does in the cell

BRAF contains the blueprint for a kinase, an enzyme that switches other proteins on by attaching phosphate groups to them. It is one link in a signalling chain that passes growth signals from the cell surface to the nucleus: when a growth factor binds to its receptor, the switch protein RAS is activated first and switches on BRAF; BRAF activates MEK, MEK activates ERK, and ERK switches on genes for cell division and renewal in the nucleus. Normally this chain runs only as long as the external signal lasts and then switches itself off again. In the gut lining, which renews itself constantly, this pathway helps control when cells divide.

What does the BRAF V600E mutation change in how the cell works?

In V600E, position 600 of the enzyme has glutamate instead of valine. The negatively charged amino acid mimics the signal that BRAF normally only receives when it is switched on – so the enzyme stays permanently active, even without a push from RAS and without an external growth signal. The signalling chain via MEK and ERK then keeps running. This change arises during life in individual cells and is not inherited. In the large bowel it is found mainly in so-called serrated, saw-tooth-looking changes in the lining, more often in the right side of the colon, and in studies often together with increased methylation of many genes.

What detecting a BRAF mutation in stool shows

Cells from the gut lining are excreted in stool every day, and with them fragments of their DNA. If cells come from an area in which BRAF V600E has arisen, the altered gene sequence can be traced in the stool sample. Detection therefore shows that cells with this acquired change are present in the gut. It does not say where they are, how large the area is or what kind of change is involved – that can only be clarified by looking at the lining itself. Because many changes in the lining carry a different BRAF mutation or none at all, a negative result does not rule them out; this is why BRAF is examined together with other markers.

The interpretation is given in your report.