In Stage 4. Colon and Rectal Cancer, Non-V600 BRAF Mutation Indicates a Favorable Disease Course

A retrospective genetic analysis involving 9643 colon and rectal cancer patients detected BRAF mutations in 965; among these, 208 (%22) were outside codon 600. (non-V600). Thus, %2.2 of all colon and rectal cancers had non-V600 BRAF mutations. Why does this matter?

First; referring to cancers of the large intestine, colon and rectal cancers are our country's third most common cancer in both women and men. Approximately 36400 people are diagnosed annually. Non-V600 BRAF mutation thus directly concerns approximately 800 people yearly in our country alone.

Second, normally finding a BRAF mutation in a cancer indicates a more aggressive course, but detecting it also enables use of BRAF-targeted treatments vemurafenib, cobimetinib, dabrafenib and trametinib. Conversely, the study discussed here showed that patients with metastatic colon and rectal cancer carrying non-V600 BRAF mutations have a much better disease course.

According to the Study Results;

• Patients with metastatic colon and rectal cancer carrying non-V600 BRAF mutations were significantly younger, often male, and had lower tumor grades than V600E BRAF-mutated patients, with tumors tending to be located in the right colon as their site.
• Patients with non-V600 BRAF mutations had significantly more concurrent RAS mutations than V600E BRAF-mutated patients (%26 versus %2). Conversely, genomic instability expressed as microsatellite instabilitywas less common in non-V600 BRAF-mutated metastatic colorectal cancer (%6 versus %30).
• The most striking result was that non-V600 BRAF-mutated patients' overall survival was significantly longer. Median overall survival was 60.7 months with this mutation; in V600E BRAF-mutated patients, 11.4 months; and without any BRAF mutation, 43 months.

Non-V600 BRAF mutation has thus led to defining a new metastatic colorectal cancer subtype. More studies are needed to determine how non-V600 mutations should guide treatment (for example, EGFR or RAS-targeted treatments may work better in these patients).

In conclusion we must say this is a very good analysis. Understanding clues to a cancer's course is important. In metastatic colon cancer, tumor genetics provide important clues about treatment selection and success.