Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors.

Telomerase reverse transcriptase () mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether mutations can be detected in circulating cell-free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated with these mutations. We retrieved data on C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas. We measured these mutations in plasma cfDNA in 218 patients with HCC and 81 patients with cirrhosis without imaging evidence of HCC. The prevalence of mutations in The Cancer Genome Atlas HCC specimens was 44.4%. mutations were detected with similar prevalence (47.7%) in plasma cfDNAs from 218 patients with HCC. mutations, either within the HCC or in cfDNA, were associated with male sex, hepatitis C virus (HCV), alcoholic cirrhosis, family history of cancer, and poor prognosis. The high prevalence of mutations in HCCs in male patients with cirrhosis caused by HCV and/or alcohol was confirmed in an independent set of HCCs (86.6%). Finally, mutations were detected in cfDNA of 7 out of 81 (8.6%) patients with cirrhosis without imaging evidence of HCC, including 5 male patients with cirrhosis due to HCV and/or alcohol. Genes involved in xenobiotic and alcohol metabolism were enriched in HCCs with mutations, and vitamin K2 was identified as an upstream regulator. : mutations are detectable in plasma cfDNA. Long-term imaging surveillance of patients with cirrhosis with cfDNA TERT mutations without evidence of HCC is required to assess their potential as early biomarkers of HCC. ( 2018;2:718-731).