Humaid Al-Shamsi is currently working as an Assistant Professor, University of Texas MD Anderson Cancer Center and he is also positioned as an Assistant Clinical Professor (Part Time) in the Department of Oncology at McMaster University. He has been a recipient of many awards and grants. His research experience includes various programs, contributions and participation at different countries for diverse fields of study. His research interests reflect in his wide range of publications in various national and international journals. His research interests include Oncology, Radialogy, Hepatology, Clinical Oncology, etc.



Background: Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). However, expanded mutational testing often identifies mutations with unclear clinical, therapeutic or prognostic implications. One such example is BRAF mutations which occur outside of codon 600 (non-V600BRAF mutations).


Methods: We completed this multicenter, retrospective cohort study to fully characterize the clinical, pathologic and survival implications of non-V600BRAF mutations in metastatic CRC. We identified and pooled all patients with CRC in whom non-V600BRAF mutations were identified from NGS databases at three large molecular genetics reference labs.


Findings: A total of 9643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with non-V600BRAF mutations, which accounted for 21.5% of all BRAF mutations. The estimated prevalence of non-V600BRAF mutations in all patients tested was 2.2%. Cancers with non-V600BRAF compared with V600EBRAF mutations were found in patients who were significantly younger (58 vs. 68 years; p<0.0001), less likely to be female (46% vs. 65%; p=0.0008), and had less high grade (13% vs. 64%; p<0.0001), or right-sided primary tumors (36% vs. 81%; p<0.0001). Median overall survival (OS) was significantly longer in patients with non-V600BRAF mutations compared to those with V600EBRAF-mutant metastatic CRC (OS: 60.7 months vs. 11.4 months; p<0.0001). In multivariate analysis, non-V600BRAF mutation remained independently associated with improved OS (HR: 0.18; p< 0.0001).


Interpretation: Non-V600BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a new subtype of CRC with an excellent prognosis.