1. Telomerase reverse transcriptase promoter mutations in hepatitis B virus-associated hepatocellular carcinoma
- Author
-
Guorong Chen, Yao Chen, Xunjun Yang, Kate Huang, Xiuchan Guo, Yin Ma, Cheryl A. Winkler, Jianxin Lyu, Ping An, Yuning Zhang, and Qiongya Zhao
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Somatic cell ,TERT ,Biopsy ,medicine.disease_cause ,03 medical and health sciences ,Young Adult ,Asian People ,Biomarkers, Tumor ,Medicine ,Humans ,Telomerase reverse transcriptase ,Family history ,Promoter Regions, Genetic ,neoplasms ,Telomerase ,Aged ,Aged, 80 and over ,business.industry ,Liver Neoplasms ,telomerase reverse transcriptase ,hepatocellular carcinoma ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Hepatitis B ,Virology ,digestive system diseases ,030104 developmental biology ,Oncology ,Hepatocellular carcinoma ,Mutation ,Medical genetics ,Christian ministry ,Female ,alpha-Fetoproteins ,business ,National laboratory ,Research Paper - Abstract
// Xunjun Yang 1, 2 , Xiuchan Guo 1, 3 , Yao Chen 4 , Guorong Chen 4 , Yin Ma 1 , Kate Huang 4 , Yuning Zhang 1 , Qiongya Zhao 1 , Cheryl A. Winkler 5 , Ping An 5 , Jianxin Lyu 1 1 Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China 2 Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 3 ICF International, Atlanta, GA, USA 4 Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 5 Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA Correspondence to: Ping An, email: anp@mail.nih.gov Jianxin Lyu, email: ljx@wmu.edu.cn Keywords: hepatocellular carcinoma, TERT, mutation, telomerase reverse transcriptase Received: February 01, 2016 Accepted: March 28, 2016 Published: April 1, 2016 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.
- Published
- 2016