Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection

Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early even...

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Main Authors: Renan da Silva Santos, Daniel Pascoalino Pinheiro, Carlos Gustavo Hirth, Maria Júlia Barbosa Bezerra, Isabelle Joyce de Lima Silva-Fernandes, Francisca Andréa da Silva Oliveira, Maisa Viana de Holanda Barros, Ester Silveira Ramos, Arlindo A. Moura, Manoel Odorico de Moraes Filho, Claudia Pessoa, Cristiana Libardi Miranda Furtado
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Epigenetics
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Online Access:https://www.tandfonline.com/doi/10.1080/15592294.2024.2305081
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author Renan da Silva Santos
Daniel Pascoalino Pinheiro
Carlos Gustavo Hirth
Maria Júlia Barbosa Bezerra
Isabelle Joyce de Lima Silva-Fernandes
Francisca Andréa da Silva Oliveira
Maisa Viana de Holanda Barros
Ester Silveira Ramos
Arlindo A. Moura
Manoel Odorico de Moraes Filho
Claudia Pessoa
Cristiana Libardi Miranda Furtado
author_facet Renan da Silva Santos
Daniel Pascoalino Pinheiro
Carlos Gustavo Hirth
Maria Júlia Barbosa Bezerra
Isabelle Joyce de Lima Silva-Fernandes
Francisca Andréa da Silva Oliveira
Maisa Viana de Holanda Barros
Ester Silveira Ramos
Arlindo A. Moura
Manoel Odorico de Moraes Filho
Claudia Pessoa
Cristiana Libardi Miranda Furtado
author_sort Renan da Silva Santos
collection DOAJ
description Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16INK4a+ (p = 0.59) and high-risk HPV+ (p = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16INK4a+ or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR (p = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.
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spelling doaj-art-f061f9d4003345e9ba09a617978bc1762024-12-09T07:21:36ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2024.2305081Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infectionRenan da Silva Santos0Daniel Pascoalino Pinheiro1Carlos Gustavo Hirth2Maria Júlia Barbosa Bezerra3Isabelle Joyce de Lima Silva-Fernandes4Francisca Andréa da Silva Oliveira5Maisa Viana de Holanda Barros6Ester Silveira Ramos7Arlindo A. Moura8Manoel Odorico de Moraes Filho9Claudia Pessoa10Cristiana Libardi Miranda Furtado11Department of Physiology and Pharmacology, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, BrazilOswaldo Cruz Foundation, FIOCRUZ-Ceará, Sector of Biotechnology, Eusebio, Ceará, BrazilLaboratory of Pathology, Cancer Institute of Ceará, Fortaleza, Ceará, BrazilLaboratory of Molecular Biology and Genetics, Cancer Institute of Ceará, Fortaleza, Ceará, BrazilLaboratory of Molecular Biology and Genetics, Cancer Institute of Ceará, Fortaleza, Ceará, BrazilGenomics and Bioinformatics Center, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, BrazilPostgraduate Program in Translational Medicine, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, BrazilDepartment of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, BrazilDepartment of Physiology and Pharmacology, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, BrazilDepartment of Physiology and Pharmacology, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, BrazilDepartment of Physiology and Pharmacology, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, BrazilPostgraduate Program in Translational Medicine, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, BrazilPenile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16INK4a+ (p = 0.59) and high-risk HPV+ (p = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16INK4a+ or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR (p = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.https://www.tandfonline.com/doi/10.1080/15592294.2024.2305081Penile squamous cell carcinomahuman papillomavirusH19DMRhypomethylationgenomic imprintingsingle nucleotide polymorphism
spellingShingle Renan da Silva Santos
Daniel Pascoalino Pinheiro
Carlos Gustavo Hirth
Maria Júlia Barbosa Bezerra
Isabelle Joyce de Lima Silva-Fernandes
Francisca Andréa da Silva Oliveira
Maisa Viana de Holanda Barros
Ester Silveira Ramos
Arlindo A. Moura
Manoel Odorico de Moraes Filho
Claudia Pessoa
Cristiana Libardi Miranda Furtado
Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection
Epigenetics
Penile squamous cell carcinoma
human papillomavirus
H19DMR
hypomethylation
genomic imprinting
single nucleotide polymorphism
title Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection
title_full Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection
title_fullStr Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection
title_full_unstemmed Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection
title_short Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection
title_sort hypomethylation at h19dmr in penile squamous cell carcinoma is not related to hpv infection
topic Penile squamous cell carcinoma
human papillomavirus
H19DMR
hypomethylation
genomic imprinting
single nucleotide polymorphism
url https://www.tandfonline.com/doi/10.1080/15592294.2024.2305081
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