Abstract
It is well known that both the mutation and integration of the Hepatitis B virus (HBV) are of great significance in liver cancer, however, the relationship between mutation and integration is still unclear. In the present study, sequencing data from 426 previously published samples were analyzed and 5374 specific HBV mutations in cancer tissues were discovered. By comparing integrated samples and non-integrated samples, we found that the integrated samples had higher sample single nucleotide variants (SNVs) positive rates and SNV numbers, as well as higher sample frequency of SNV in the X region of the HBV genome. Samples with HBV integration in the telomerase reverse transcriptase (TERT) region showed higher SNV positive rates and numbers than samples without integration. Moreover, the SNVs (209 [T>G] and 531 [T>C; T>G]) were seen with higher frequency in samples with integration in the TERT region. Our study showed that the occurrence of viral integration events is closely related to the occurrence of SNV, and SNV in the X region should be more directly associated with viral integration. The present study provides an initial exploration of the relationship between HBV mutation and integration to help improve our understanding of the relationship between viral integration and mutation.
Highlights
Chronic infection caused by the Hepatitis B virus (HBV) is a global public health problem, with approximately 350 million people suffering from it, among which 75% are Asians [1,2]
Comparing the samples with and without HBV integration on telomerase reverse transcriptase (TERT), the results showed that the samples with HBV integration on the TERT region had a higher single nucleotide variant (SNV) sample frequency (Supplementary Tables S3–S5, Figure 3B, P
The present study found that positive samples of viral integration have a higher positive SNV rate, and that integrated samples in the TERT region have a very high SNV positive rate
Summary
Chronic infection caused by the Hepatitis B virus (HBV) is a global public health problem, with approximately 350 million people suffering from it, among which 75% are Asians [1,2]. [3] Genotype is an important biological feature of HBV and different genotypes/subtypes will have different pathogenic characteristics. Genotype B often causes acute infection, while genotype C often leads to chronic infection, and subtype C is a key risk factor for the occurrence of HCC. The mutations that occur during the HBV replication process contribute to the evolutionary characteristics of clonal selection and these mutations are closely related to the progression of hepatitis B-related diseases [4,5]. HBV carriers are 5–15-times more likely to develop cancer than non-carriers and the occurrence of HBV integration is correlated with an increased risk of cancer [6,7]. It is clear that viral integration events have an important influence on tumorigenesis [11]
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