Investigation of EGFR and KRAS mutation changes in peripheral blood cfDNA specimens after first line therapy of lung adenocarcinoma patients.
Project no. 70 · Status: Kapanmış · 2017
Summary
The presence of oncogene mutations observed in about half of lung adenocarcinomas is important in terms of targeted treatment and prognosis. Oncogenic mutation detection is based on samples of tumor tissue taken by biopsy. Tumor biopsy cannot be performed in all patients and it is a time consuming and invasive procedure that requires expertise. In addition, tumor biopsy reflects only the biopsy site and does not reflect intra and inter tumor heterogeneity. There is little chance of repeat the follow-up of the tumor during the treatment process. In recent years, it has been possible to detect oncogene mutations by collecting cell-free DNA (cfDNA) called liquid biopsy. Liquid biopsy specimen reflects tumor burden and heterogeneity, is minimally invasive and can be repeated at any time and frequency in all patients. In this project, we aimed to obtain information that can contribute to treatment and prognosis by comparing oncogene changes, mutation changes, mutation burden changes, the mutation associated with tumor before and after first-line therapy, relation of tumor with new formations, metastasis relationships, and treatment response. Fifty-two cases with adenocarcinoma of lung were included in the study. 123 mutations observed in EGFR, KRAS, BRAF, NRAS, and PIK3CA oncogenes were investigated by Allel Specific PCR (AS-PCR) method. In 29 of the cases, no mutations were detected before and after the treatment, while 39 mutations were detected, of which 23 had at least one mutation. There were 3 different mutations in one case, 2 mutations in 4 cases and one mutation in 18 cases. In 3 cases where no mutation was detected before treatment, post-treatment mutation was detected in 5 cases, whereas in 5 cases there was no post-treatment mutation. In 15 cases with mutation, mutation burden changes were detected before and after treatment. One patient with NRAS mutation had KRAS mutations after treatment. The cases with EGFR mutation responded well to the treatment and the EGFR mutations decreased to an undetectable level after tumor regression. KRAS codon 59, 117, 146 mutations, which are rarely observed in the literature, were detected as high as 7.5% in our study. It was observed that these mutations showed multiple mutation associations, tumor centers were necrosis and they were located especially in the upper lobe of the right lung. It was observed that patients with KRAS codon 12 mutation having better treatment response than patients with KRAS codon 13 mutation, did not show mutation associations, and were located outside the upper lobe of the right lung. It was found that the primary tumor of the central location did not show distant metastasis, and caused a poor prognosis with intra-pulmonary spread. It was observed that the cases with bone metastasis were concentrated in the right lung, the cases with primary tumor in the right lung were tend to metastasize to the right adrenal gland, and the left ones to the left adrenal gland. The findings were supported by studies involving more cases.