USE OF CIRCULATING TUMOR DNA FOR DETECTION OF BRAF V600E MUTATION AND TREATMENT MONITORING IN MELANOMA PATIENTS.

Detection of BRAF V600E mutation in circulating tumor DNA may be important tool for primary diagnostic and therapeutic monitoring in patients with melanoma. For the first time in Ukraine, the sensitivity of BRAF V600E testing on circulating tumor DNA was analyzed, as well as the possibility of its application for monitoring the course of the disease. Allele-specific semi-quantitative Real-time PCR for BRAF V600E mutation was performed on DNA extracted from 28 plasma samples of 18 patients with known BRAF V600E melanoma. At baseline, BRAF V600E ctDNA was detected in 67% of all patients (n=11/17) and in 75% (n=11/15) of patients with IV stage. In 7 cases we have more than one blood sample from patient. In 2 of 3 patients with positive BRAF V600E ctDNA at the baseline, mutation became undetectable during therapy that was associated with stable disease and partial response. In 2 cases patients had stage II and after surgery BRAF V600E ctDNA was undetectable, but then mutation was detected prior to clinical disease progression (PD) in one case and simultaneously with PD in another. One patient with resected brain metastasis of melanoma with unknown primary also had negative baseline and second sample (after 5 months) but BRAF V600E was detected in third sample (after 11 months) without radiological evidence of progression. ctDNA in plasma is a good source for BRAF V600E primary testing in case of absence or low quality of FFPE tissue and potential instrument for monitoring of disease flowing. Its potential role in management of patients with malignant melanoma requires further evaluation.