title: Telomerase reverse transcriptase promoter mutations in hepatitis B virus-associated hepatocellular carcinoma.
abstract: Telomerase reverse transcriptase (TERT) promoter mutations are among the most frequent noncoding somatic mutations in multiple cancers, including hepatocellular carcinoma (HCC). The clinical and pathological implications of TERT promoter mutations in hepatitis B virus (HBV)-associated HCC have not been resolved. To investigate TERT promoter mutations, protein expression, and their clinical-pathological implications, we sequenced the TERT promoter region for hotspot mutations in HCC tissues and performed immunostaining for TERT protein expression from HBV-associated HCC in Chinese patients. Of 276 HCC tumor DNA samples sequenced, 85 (31%) carried TERT promoter mutations. TERT promoter mutations were more frequent in those with low α-fetoprotein (AFP) serum levels (p = 0.03), advanced age (p = 0.04), and in those lacking HCC family history (p = 0.02), but were not correlated with HCC stages and grades. TERT protein levels were higher in HCC (n = 28) compared to normal liver tissues (n = 8) (p =0.001), but did not differ between mutated and non-mutated tumor tissues. In conclusion, TERT promoter mutations are common somatic mutations in HCC of Han Chinese with HBV infection. Detection of TERT promoter mutations in those with low levels of AFP may aid diagnosis of HCC with atypical presentation.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.|Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xunjun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.|ICF International, Atlanta, GA, USA.
authors.forename: Xiuchan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Kate
authors.initials: K
authors.lastname: Huang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Qiongya
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lyu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000235:genetics* / Q000821:virology; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; C509186:TERT protein, human; D019098:Telomerase
keywords: TERT; hepatocellular carcinoma; mutation; telomerase reverse transcriptase