Polymorphic variability in the exon 19 of the RB1 gene and its flanking intronic sequences in HPV16-associated precancerous lesions in the Greek population

Tsakogiannis, D.; Moschonas, George D.; Daskou, M.; Stylianidou, Zoe; Kyriakopoulou, Zaharoula; Kottaridi, Christine; Dimitriou, Tilemachos G.; Gartzonika, Constantina; Markoulatos, Panayotis

doi:10.1099/jmm.0.000843

Cited by 4 publications

(3 citation statements)

References 45 publications

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“…However, we cannot exclude the possibility that this theory might be applicable for HPV16 in the future. Additional factors should be taken into consideration in order to lead to more accurate conclusions about cervical cancer risk, such as multiple HR-HPV infections, viral DNA integration, the methylation status of HPV DNA and mutations into the host target proteins ( Refs 13,18,34,[158][159][160].…”

Section: Discussionmentioning

confidence: 99%

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Bletsa¹,

Zagouri

Amoutzias

et al. 2021

Expert Rev. Mol. Med.

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Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6 : Q14H, H78Y, L83V, Ε7 : N29S, S63F, E2 : H35Q, P219S, T310K, E5 : I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

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Section: Discussionmentioning

confidence: 99%

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Bletsa¹,

Zagouri

Amoutzias

et al. 2021

Expert Rev. Mol. Med.

Self Cite

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“…Rb (retinoblastoma gene) is one of the most representative TSGs. It plays a regulation role in three processes: cell cycle control, apoptosis, and differentiation (10,11). Hypermethylation of the Rb promoter region has been reported in hepatocellular carcinoma and gastric cancer (12,13) This shows that this feature produces modification in the cell cycle and proliferation of both neoplasms (11,14).…”

Section: Introductionmentioning

confidence: 99%

Methylation Analysis of Rb, P16, MGMT, and hMLH-1in Mucoepidermoid Carcinomas. A Pilot Study

Martínez-Marcial

Jacinto-Alemán²,

Trejo-Remigio³

et al. 2022

Odovtos - Int J Dent Sc

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Mucoepidermoid carcinoma (MC) is the most common malignant epithelial neoplasm in the salivary glands. This neoplasm has varying proportions of mucous, epidermoid, intermediate, columnar, and clear cells. MCs have been associated with CRTC1-MAML2 genes; however, their pathogenesis is uncertain. Recently, epigenetic changes have been considered a possible aetiologic factor. To identify the methylation state of RB, P16, MGMT, and hMLH genes in the three severity grades of MC were used five MCs and one healthy minor salivary gland as a control group (CG) obtained from the Pathology and Oral Medicine Laboratory and analyzed using MS-PCR to compare the presence or absence of methylation in promotor regions. The Kruskal-Wallis test was performed, with p≤0.05 considered significant. CG was employed as the normalizer of methylation levels. All assays were performed in triplicate. The mean age of our population was 52.6±18.6 years old; the total population was female and included 2 low grade, 2 intermediate grade, and 1 high grade levels of severity. When comparing the methylation status of the three histopathological grades of MC against the control, statistically significant differences were observed in Rb-M, MGMT-M, and hMLH-1-NM for high-grade severity, with p values of 0.03, 0.05, and 0.04, respectively. Methylation is a possible mechanism for pathogenesis processing of high-grade MC. However, a larger sample population is necessary to validate this finding.

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“…Accordingly, the E7 oncorotein interacts with pRb and releases the E2F transcription factor from the pRB/E2F suppressor complex. The disruption of the pRB/E2F complex enables the stimulation of the mitotic phase of cell cycle and consequently triggers cell proliferation [ 25 , 26 ]. An additional mechanism that is strongly implicated in viral carcinogenicity is the integration of HPV DNA into the host genome.…”

Section: Introductionmentioning

confidence: 99%

Mutation Profile of HPV16 L1 and L2 Genes in Different Geographic Areas

Tsakogiannis¹,

Nikolaidis

Zagouri

et al. 2022

Viruses

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The causal relationship between HPV and cervical cancer in association with the high prevalence of high risk HPV genotypes led to the design of HPV vaccines based on the major capsid L1 protein. In recent years, capsid protein L2 has also become a focal point in the field of vaccine research. The present review focuses on the variability of HPV16 L1 and L2 genes, emphasizing the distribution of specific amino acid changes in the epitopes of capsid proteins. Moreover, a substantial bioinformatics analysis was conducted to describe the worldwide distribution of amino acid substitutions throughout HPV16 L1, L2 proteins. Five amino acid changes (T176N, N181T; EF loop), (T266A; FG loop), (T353P, T389S; HI loop) are frequently observed in the L1 hypervariable surface loops, while two amino acid substitutions (D43E, S122P) are adjacent to L2 specific epitopes. These changes have a high prevalence in certain geographic regions. The present review suggests that the extensive analysis of the amino acid substitutions in the HPV16 L1 immunodominant loops may provide insights concerning the ability of the virus in evading host immune response in certain populations. The genetic variability of the HPV16 L1 and L2 epitopes should be extensively analyzed in a given population.

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Polymorphic variability in the exon 19 of the RB1 gene and its flanking intronic sequences in HPV16-associated precancerous lesions in the Greek population

Cited by 4 publications

References 45 publications

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Methylation Analysis of Rb, P16, MGMT, and hMLH-1in Mucoepidermoid Carcinomas. A Pilot Study

Mutation Profile of HPV16 L1 and L2 Genes in Different Geographic Areas

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