Identification of circulating tumour DNA (ctDNA) from the liquid biopsy results: Findings from an observational cohort study

Abstract

Liquid biopsies can be a rapid, cost-effective and non-invasive alternative to tumour biopsies for detecting genetic mutations in somatic tumours. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their distribution in a small study cohort. We studied the genomic profiles of 99 blood samples from 85 patients with 21 different types of cancer using two commercially available liquid biopsy tests. The mean circulating free DNA (cfDNA) concentration was 162.7 ± 352.3 nanograms per 20 millilitres. Amongst cfDNA, the circulating tumour DNA (ctDNA) percentage ranged from 0.006% to 90.6%. With the exception of samples with gene amplification and high microsatellite instability, the number of mutations in each sample varied from zero to 21, with an average of 5.6 mutations in each patient. Amongst these mutations, nonsynonymous mutations were the most frequently observed type of mutation (90% of the sample, with an average frequency of 3.6 mutations per patient). Mutations were observed in 76 different genes. TP53 mutations constituted more than 16% of the detectable mutations, especially in non-small cell lung cancer. All the tumour types, except the ovary, kidney and apocrine gland tumours, harboured at least one type of TP53 mutation. KRAS (mainly in pancreatic cancer) and PIK3CA (mostly in breast cancer) mutations, were responsible for an additional 10% of the mutations in the studied samples. The tumour mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication amongst the patients. These findings indicate that liquid biopsy can detect specific molecular changes of tumour, which is useful for precision oncology and personalized cancer treatment.