Clinicopathological aspects of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutated non-small cell lung carcinoma in an Indian cohort: is there a difference?

Introduction: Activating mutations in the BRAF gene have been reported in 0.8%-8% cases of NSCLC. Traditionally, diagnostics have mainly focused on detection of V600E and modalities like mutation specific IHC, allele specific real-time PCR have been utilized. This may underestimate true prevalence of the non-V600E variants. Broader panel NGS testing offers a one stop solution and may identify newer potentially targetable variants. This is a retrospective single center experience of patients with BRAF mutated NSCLC characterizing the molecular spectrum and clinicopathologic characteristics.

Methods: 260 patients underwent panel based NGS testing at our center, between 2017-2020. 13 BRAF mutant cases, were detected and were clinically reviewed.

Results: Thirteen cases of BRAF alterations were seen in out of 260 (5%) patients. Median age of the cohort was 62 years (range: 39-86 years) with a female predilection). Canonical BRAF V600E mutation was seen in 6 (46.2%) patients and 7 (53.8%) harbored a non-V600E alteration. Spectrum of non V600E alterations included G466E, G469A, N581I, V600_K601delins, D594G, L597Q, G649V and were commonly female (P>0.01) with a higher trend for liver metastases (P=0.09). Median PFS was 4.8 months on chemotherapy (P=0.8). All patients (13/13, 100%) were never smokers with an adenocarcinoma histology.

Conclusion: This is a single center experience from an Indian NSCLC cohort and shows higher prevalence of non-V600E than V600E mutation reported in literature. This may be attributed to increased use of NGS testing revealing otherwise missed alterations on sequential single gene testing.