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.
Epigenetics. 2024 Jan 21 [Epub]
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, Odorico de Moraes Manoel Filho, Claudia Pessoa, Cristiana Libardi Miranda Furtado
Department of Physiology and Pharmacology, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, Brazil., Oswaldo Cruz Foundation, FIOCRUZ-Ceará, Sector of Biotechnology, Eusebio, Ceará, Brazil., Laboratory of Pathology, Cancer Institute of Ceará, Fortaleza, Ceará, Brazil., Laboratory of Molecular Biology and Genetics, Cancer Institute of Ceará, Fortaleza, Ceará, Brazil., Genomics and Bioinformatics Center, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, Brazil., Postgraduate Program in Translational Medicine, Drug Research and Development Center, Federal University of Ceará, Fortaleza, Ceará, Brazil., Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.