Mutation concordance of matched tissue sample and blood sample: A result of 456 lung cancer patients.

Abstract

e20049 Background: Cell-free DNA (cfDNA) sequencing is an important alternative for tissue sequencing when tissue samples are not available. To better study the association of a blood sample and tissue sample, we designed a study to evaluate the concordance of gene mutations of tumor tissues and matched cfDNA. Methods: From May 2017 to January 2019, 456 lung cancer patients were enrolled in this study. For each patient, a matched tumor tissue sample and blood sample were collected. DNA samples were extracted from these samples, and then sequenced with a pan-cancer gene panel. Results: The concordance ratio was computed by the number of common variants divided by the summation of common variants, the number of tissue-specific variants and number of blood-specific variants. Among these 456 patients, an overall by-variant concordance ratio of 49.7% (1457/2932) was observed. When considering only the major driver genes, the observed concordance ratios were EGFR = 45.7% (96/210), KRAS = 48.5% (147/303), ALK-fusion = 50% (8/16) and BRAF = 52.5% (21/40). The mean variant allele frequency (VAF) of common variants was significantly higher than the mean VAF of variants only detected in tissue (29.07% vs. 12.29%, p-value < 2.2e-16). Conclusions: This study shows that the concordance ratio between a tissue sample and a blood sample is close to 50%. As new technologies are being developed to detect low-frequency variants better, we can expect this concordance ratio to improve in the future.