Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors.
Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors.
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DOI：
10.1002/hep4.1187
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发表时间：
2018-06
影响因子：
5.1
通讯作者：
Beretta L
中科院分区：
文献类型：
--
作者：
Jiao J;Watt GP;Stevenson HL;Calderone TL;Fisher-Hoch SP;Ye Y;Wu X;Vierling JM;Beretta L
端粒酶逆转录酶（TERT）突变是肝细胞癌（HCC）中最常见的基因改变。我们的目的是研究是否可以在HCC和/或肝硬化患者的循环无细胞DNA（cfDNA）中检测到TERT突变，并表征与这些突变相关的临床参数。我们从癌症基因组图谱中检索了196例HCC中关于TERT C228 T和C250 T启动子突变的数据。我们测量了218例HCC患者和81例无HCC影像学证据的肝硬化患者血浆cfDNA中的这些TERT突变。癌症基因组图谱HCC标本中TERT突变的患病率为44.4%。在来自218名HCC患者的血浆cfDNA中检测到具有相似患病率（47.7%）的TERT突变。HCC或cfDNA中的TERT突变与男性、丙型肝炎病毒（HCV）、酒精性肝硬化、癌症家族史和不良预后相关。在一组独立的HCC（86.6%）中证实了HCV和/或酒精所致肝硬化男性患者HCC中TERT突变的高患病率。最后，在81名没有HCC影像学证据的肝硬化患者中的7名（8.6%）的cfDNA中检测到TERT突变，其中包括5名因HCV和/或酒精导致肝硬化的男性患者。参与外源性物质和酒精代谢的基因在具有TERT突变的HCC中富集，并且维生素K2被鉴定为上游调节剂。结论：血浆cfDNA中可检测到TERT突变。需要对具有cfDNA TERT突变但无HCC证据的肝硬化患者进行长期成像监测，以评估其作为HCC早期生物标志物的潜力。（Hepatology Communications 2018;2：718 - 731）
Telomerase reverse transcriptase (TERT) mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether TERT 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 TERT C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas. We measured these TERT mutations in plasma cfDNA in 218 patients with HCC and 81 patients with cirrhosis without imaging evidence of HCC. The prevalence of TERT mutations in The Cancer Genome Atlas HCC specimens was 44.4%. TERT mutations were detected with similar prevalence (47.7%) in plasma cfDNAs from 218 patients with HCC. TERT 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 TERT 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, TERT 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 TERT mutations, and vitamin K2 was identified as an upstream regulator. Conclusion: TERT 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. (Hepatology Communications 2018;2:718‐731)
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影响因子：
--
作者：
Liao W;Yang H;Xu H;Wang Y;Ge P;Ren J;Xu W;Lu X;Sang X;Zhong S;Zhang H;Mao Y
通讯作者：
Mao Y
1975年至2012年，向国家报告癌症状况的年度报告，其发病率不断增加。
影响因子：
6.2
作者：
Ryerson AB;Eheman CR;Altekruse SF;Ward JW;Jemal A;Sherman RL;Henley SJ;Holtzman D;Lake A;Noone AM;Anderson RN;Ma J;Ly KN;Cronin KA;Penberthy L;Kohler BA
通讯作者：
Kohler BA
使用微滴式数字 PCR 检测肝细胞癌患者的循环肿瘤 DNA 是可行的，并反映了瘤内异质性
影响因子：
3.9
作者：
Huang A;Zhang X;Zhou SL;Cao Y;Huang XW;Fan J;Yang XR;Zhou J
通讯作者：
Zhou J
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
3.5
作者：
Hamitouche, S.;Poupon, J.;Lucas, D.
通讯作者：
Lucas, D.