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Sequencing Analysis of Plasma Epstein-Barr Virus DNA Reveals Nasopharyngeal Carcinoma-Associated Single Nucleotide Variant Profiles
- Source :
- Clinical Chemistry. 66:598-605
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- Background Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. Plasma EBV DNA is a validated screening tool for NPC. In screening, there are some individuals who do not have NPC but carry EBV DNA in plasma. Currently it is not known from screening if there may be any genotypic differences in EBV isolates from NPC and non-NPC subjects. Also, low concentrations of EBV DNA in plasma could pose challenge to such EBV genotypic analysis through plasma DNA sequencing. Methods In a training dataset comprised of plasma DNA sequencing data of NPC and non-NPC subjects, we studied the difference in the EBV single nucleotide variant (SNV) profiles between the two groups. The most differentiating SNVs across the EBV genome were identified. We proposed an NPC risk score to be derived from the genotypic patterns over these SNV sites. We subsequently analyzed the NPC risk scores in a testing set. Results A total of 661 significant SNVs across the EBV genome were identified from the training set. In the testing set, NPC plasma samples were shown to have high NPC risk scores, which suggested the presence of NPC-associated EBV SNV profiles. Among the non-NPC samples, there was a wide range of NPC risk scores. These results support the presence of diverse SNV profiles of EBV isolates from non-NPC subjects. Conclusion EBV genotypic analysis is feasible through plasma DNA sequencing. The NPC risk score may be used to inform the cancer risk based on the EBV genome-wide SNV profile.
- Subjects :
- 0301 basic medicine
Epstein-Barr Virus Infections
Herpesvirus 4, Human
Genotype
Clinical Biochemistry
Genome, Viral
Biology
medicine.disease_cause
Models, Biological
Polymorphism, Single Nucleotide
Genome
Virus
03 medical and health sciences
0302 clinical medicine
Risk Factors
otorhinolaryngologic diseases
medicine
Humans
Nucleotide
chemistry.chemical_classification
Nasopharyngeal Carcinoma
Training set
Biochemistry (medical)
Epstein-Barr virus DNA
Sequence Analysis, DNA
medicine.disease
Virology
Epstein–Barr virus
stomatognathic diseases
030104 developmental biology
chemistry
Nasopharyngeal carcinoma
030220 oncology & carcinogenesis
DNA, Viral
Subjects
Details
- ISSN :
- 15308561 and 00099147
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Clinical Chemistry
- Accession number :
- edsair.doi.dedup.....c65698e292b0f1ce4d63711bacbd2e80