HPV16 E2 variants correlated with radiotherapy treatment and biological significance in cervical cell carcinoma.
Infect Genet Evol
; 65: 238-243, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30081093
Specific genetic mutations in human papillomavirus type 16 (HPV16) DNA are considered important in cervical lesion progression. This study analyzes to what extent radiotherapy treatment contributes to viral DNA mutation in cervical cell carcinomas, and the biological significance of these mutations. Serial tumor tissue, including 44 cervical cancer samples, collected before and after radiotherapy, and 52 biopsies with benign cervices, were tested and analyzed for the presence of HPV16, and for the integrity of the E2 gene. Analysis was performed with polymerase chain reaction (PCR), and a bidirectional sequencing assay was performed to find HPV16 E2 gene variants. HPV16 E2 accounted for 81.8% and 37.5% among tumor and benign cervices respectively (pâ¯=â¯0.02). The incremental number of DNA mutations was associated with radiotherapy treatment. Most E2 gene mutations involved regions encoding the amino-terminal and carboxy-terminal regions of E2 in the tumor irradiated samples. Amino acid changes T135â¯K, A143T, N203D and P208A in the amino-terminal region were the most common mutations across the irradiated samples. Rather, the mutations in the carboxy-terminal region (T3694A and T3805G) were synonymous changes. Specific nucleotide deletions were detected in the hinge domain, at positions 3455Aâ¯>â¯-, 3466â¯Tâ¯>â¯-, and 3501Aâ¯>â¯-. The mutation degree is influenced by the irradiation modalities, interestingly E2 sequence mutation being found widely after radiotherapy treatment with a total fractioned dose of 50â¯Gy (pâ¯=â¯0.004). E2 mutation has predictive and biological significance in cervical cancer patients receiving curative radiation therapy. Possibly, E2 mutation could influence viral genome intactness and could serve as an intrinsic marker for cervical cancer.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias del Cuello Uterino
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Proteínas Oncogénicas Virales
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Proteínas de Unión al ADN
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Papillomavirus Humano 16
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Mutación
Tipo de estudio:
Observational_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Middle aged
País/Región como asunto:
Africa
Idioma:
En
Revista:
Infect Genet Evol
Asunto de la revista:
BIOLOGIA
/
DOENCAS TRANSMISSIVEIS
/
GENETICA
Año:
2018
Tipo del documento:
Article