The association of blood ctDNA levels to mutations of marker genes in colorectal cancer

BACKGROUND: Colorectal cancer (CRC) is a deadly and commonly diagnosed cancer. Cell‐free circulating tumor DNAs (ctDNA) have been used in the diagnosis and treatment of CRC, but there are open questions about the relationship between ctDNAs and CRC. Although mutations of genes detected by ctDNA in CRC have been studied, the quantitative relationship between ctDNA mutations and ctDNA concentration has not been addressed. AIMS: We hypothesized that there was an association between mutations of genes identified in ctDNAs and ctDNA concentration. His study examined this association in a population of CRC patients. METHODS: In 85 CRC patients, we sampled 282 mutations in 36 genes and conducted an association study based on a Random forest model between mutations and ctDNA concentrations in all patients. RESULTS: This association study showed that mutations on five genes, ALK, PMS2, KDR, MAP2K1, and MSH2, were associated with the ctDNA concentrations in CRC patients’ blood samples. Because ctDNA mutations correlate with ctDNA level, we can infer the tumor burden or tumor size from ctDNA mutations, as well as the survival time for prognosis. CONCLUSION: Our findings shed light on the associations between mutations of genes identified in ctDNAs and ctDNA concentration in the blood of CRC patients. This discovery provides information regarding the tumor burden or tumor size based on ctDNA mutations.