Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Cell-Free DNA in Stage I-IV Non-Small Cell Lung Cancer

摘要

Molecular biomarkers hold promise for personalization of cancer treatment. However, a typical tumor biopsy may be difficult to acquire and may not capture genetic variations within or across tumors. Given these limitations, tumor genotyping using next-generation sequencing of plasma-derived circulating tumor (ct)-DNA has the potential to transform non-small cell lung cancer (NSCLC) management. Importantly, mutations detected in biopsied tissue must also be detected in plasma-derived ctDNA at different disease stages. Using the AVENIO ctDNA Surveillance kit (research use only), mutations in ctDNA from NSCLC subjects were compared with those identified in matched tumor tissue samples, retrospectively. Plasma and tissue samples were collected from 141 treatment-naive NSCLC subjects (stage I, n = 48; stage II, n = 37; stage III, n = 33; stage IV, n = 23). In plasma samples, the median numbers of variants per subject were 4, 6, 8, and 9 in those with stage I, II, III, and IV disease, respectively. The corresponding values in tissue samples were 5, 5, 6, and 4. The overall tissue-plasma concordance of stage II through IV was 62.2% by AVENIO software call. On multivariate analysis, concordance was positively and significantly associated with tumor size and cancer stage. Next-generation sequencing-based analyses with the AVENIO ctDNA Surveillance kit could be an alternative approach to detecting genetic variations in plasma-derived ctDNA isolated from NSCLC subjects.