BRAF V600E mutations in right-side colon cancer: Heterogeneity detected by liquid biopsy

Abstract

Introduction: The prognosis for metastatic colorectal cancer patients (mCRC) with the BRAF^V600E mutation is poor. BRAF^V600E mutation frequency is reportedly low among Asians; however, the frequency of the BRAF^V600E mutation in right-side colon cancer may not be low, even among Asians. In addition, spatial heterogeneity of BRAF^V600E mutations also exists, as for RAS mutations. In this prospective observational study, we evaluated BRAF^V600E mutations in cancer tissue and plasma of Japanese right-side colon cancer patients.

Method: 215 patients with right-side colon cancer were included. BRAF^V600E mutations of cancer tissue and plasma were detected using droplet digital PCR. Blood plasma of patients with BRAF^V600E mutations in cancer tissue or plasma was drawn at intervals throughout chemotherapy, and BRAF^V600E mutations were evaluated.

Results: BRAF^V600E mutations were detected in tissue samples from 35 of 215 patients (16.3%, cecum; 22.4%, ascending colon; 17.8%, and transverse colon; 9.0%). BRAF^V600E mutations were detected in plasma of 10 of 215 (4.7%) patients. Eight of the ten patients had BRAF^V600E mutations in their primary tumours, but two (both were Stage IV) patients did not. Sensitivity of liquid biopsy to detect BRAF^V600E mutations was 10.3% (3/29) in Stage I-III patients and 83.3% (5/6) in Stage IV patients.

Conclusion: BRAF^V600E mutations are observed in right-side colon cancer at high frequency, especially in the cecum. BRAF^V600E mutations can be detected in plasma and the detection rate is high in patients with advanced cancer. Spatial heterogeneity was observed using liquid biopsy.