Sequencing of circulating tumor DNA for dynamic monitoring of gene mutations in advanced non-small cell lung cancer.

ABSTRACT: Lung cancer is the most commonly occurring type of cancer worldwide and also has the highest mortality rate. Although targeted therapy of non-small cell lung carcinoma (NSCLC) has become common, the majority of patients receiving first-line epithelial growth factor receptor (EGFR)-TKI treatment develop drug resistance. The EGFR T790M (NM_005228.4(EGFR):c.2369C>T (p.Thr790Met)) mutation accounts for half of all reported resistance cases; however, the molecular mechanism resulting in the drug resistance remains to be characterized. Circulating tumor DNA (ctDNA) isolated from plasma has great potential for identification of gene mutations in NSCLC. Collection of ctDNA is relatively non-invasive and can avoid the inherent disadvantages of tissue biopsy. In the present study, next-generation sequencing technology was used to detect the variation of ctDNA in the peripheral blood of patients administered with EGFR-TKI. The patients were monitored serially to establish a dynamic resistance gene detection system, with the rationale being to alter the treatment strategy as soon as the emergence of drug resistance gene mutations. A mutation spectrum of the group of patients was constructed. A driver gene mutation was identified in the ctDNA of each patient, and certain patients had clinically targetable gene mutations like EGFR, ROS proto-oncogene receptor tyrosine kinase and B-Raf proto-oncogene serine/threonine kinase. The dynamic monitoring of EGFR status indicated that the EGFR mutation rate was consistent with the tumor burden of patients. Overall, ctDNA detection is a useful method for the molecular genotyping of patients with cancer. The dynamic resistance gene detection system described in the present study is a sensitive and useful tool for the monitoring of gene status, which has potential to be used for direction of treatment strategy by detecting the emergence of drug resistance gene mutations.

SUBMITTER: Xu R 

PROVIDER: S-EPMC5843997 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature