Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma

Autor: Lewis R. Roberts, Seung Kew Yoon, Si Hyun Bae, Dong Jin Han, Tae Min Kim, Jeong Won Jang, Ji Won Han, Jong Young Choi, Jin Seoub Kim, Pil Soo Sung, Soon Kyu Lee, Hye Seon Kim
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Telomerase
medicine.disease_cause
0302 clinical medicine
Viral Regulatory and Accessory Proteins
Biology (General)
Promoter Regions
Genetic
Spectroscopy
Liver Neoplasms
General Medicine
Middle Aged
Hepatitis B
Computer Science Applications
HBx
Chemistry
Hepatocellular carcinoma
030211 gastroenterology & hepatology
Female
point mutation
Adult
Carcinoma
Hepatocellular
QH301-705.5
Biology
telomerase
Catalysis
Article
Inorganic Chemistry
liver cancer
03 medical and health sciences
medicine
virus integration
Humans
Telomerase reverse transcriptase
Physical and Theoretical Chemistry
Molecular Biology
Gene
Virus Integration
QD1-999
Aged
Hepatitis B virus
Organic Chemistry
Promoter
Histone-Lysine N-Methyltransferase
medicine.disease
digestive system diseases
Fibronectins
030104 developmental biology
Case-Control Studies
DNA
Viral
Mutation
Cancer research
Trans-Activators
hepatitis B virus
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 7056, p 7056 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 13
ISSN: 1661-6596
1422-0067
Popis: Although hepatitis B virus (HBV) integration into the cellular genome is well known in HCC (hepatocellular carcinoma) patients, its biological role still remains uncertain. This study investigated the patterns of HBV integration and correlated them with TERT (telomerase reverse transcriptase) alterations in paired tumor and non-tumor tissues. Compared to those in non-tumors, tumoral integrations occurred less frequently but with higher read counts and were more preferentially observed in genic regions with significant enrichment of integration into promoters. In HBV-related tumors, TERT promoter was identified as the most frequent site (38.5% (10/26)) of HBV integration. TERT promoter mutation was observed only in tumors (24.2% (8/33)), but not in non-tumors. Only 3.00% (34/1133) of HBV integration sites were shared between tumors and non-tumors. Within the HBV genome, HBV breakpoints were distributed preferentially in the 3’ end of HBx, with more tumoral integrations detected in the preS/S region. The major genes that were recurrently affected by HBV integration included TERT and MLL4 for tumors and FN1 for non-tumors. Functional enrichment analysis of tumoral genes with integrations showed enrichment of cancer-associated genes. The patterns and functions of HBV integration are distinct between tumors and non-tumors. Tumoral integration is often enriched into both human-virus regions with oncogenic regulatory function. The characteristic genomic features of HBV integration together with TERT alteration may dysregulate the affected gene function, thereby contributing to hepatocarcinogenesis.
Databáze: OpenAIRE
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