Recent advances in next-generation sequencing have enabled the detection of BRAF V600E mutations as well as BRAF non-
V600E mutations in a single assay. The present work aimed to describe the clinicopathological characteristics and clinical outcome of the BRAF non-V600E mutant-type in colorectal cancer (CRC).
CRC samples from 111 Stage IV patients were analyzed for somatic mutations using a 415-gene comprehensive genomic sequencing panel. Patients were classified according to BRAF status as wild-type,
V600E mutant-type, or non-
V600E mutant-type. Differences between clinicopathological characteristics and genetic alterations were analyzed among the three groups. Overall survival (OS) and the response to anti-EGFR therapy were also analyzed.
Comprehensive genomic sequencing revealed that 98 patients (88%), 7 patients (6%), and 6 patients (6%) were wild-type, V600E mutant-type, and non-V600E mutant-type, respectively. Non-
V600E mutant-type tumors were frequently left-sided (83%), while
V600E mutant-type tumors were frequently right-sided (86%; P = 0.025). Non-
V600E mutant-type showed better OS than
V600E mutant-type (P = 0.038), with no significant difference compared with wild-type tumors. The two patients with non-V600E mutations who underwent repeated metastasectomies showed no evidence of disease at final follow-up. Regarding the efficacy of anti-EGFR therapy, the patient with an I326V mutation had progressive disease (+115%) despite no genetic alterations detected in the EGFR pathway that could drive resistance, suggesting an alternate resistance mechanism.
Non-
V600E mutant-type is more likely to be left-sided and demonstrates better OS than
V600E mutant-type. Further preclinical and clinical investigations are needed to clarify the role of non-V600E mutations in CRC.