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. 2024 Dec;19(1):2305081.
doi: 10.1080/15592294.2024.2305081. Epub 2024 Jan 21.

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

Renan da Silva Santos  1 , Daniel Pascoalino Pinheiro  2 , Carlos Gustavo Hirth  3 , Maria Júlia Barbosa Bezerra  4 , Isabelle Joyce de Lima Silva-Fernandes  4 , Francisca Andréa da Silva Oliveira  5 , Maisa Viana de Holanda Barros  6 , Ester Silveira Ramos  7 , Arlindo A Moura  1   8 , Odorico de Moraes Manoel Filho  1   6 , Claudia Pessoa  1 , Cristiana Libardi Miranda Furtado  6   9   10
Affiliations

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

Renan da Silva Santos et al. Epigenetics. 2024 Dec.

Abstract

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.

Keywords: H19DMR; Penile squamous cell carcinoma; genomic imprinting; human papillomavirus; hypomethylation; single nucleotide polymorphism.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Bisulfite sequencing of H19DMR in penile squamous cell carcinoma. Each row represents a sample (S) and its HPV status (positive samples were considered as p16INK4a+ or hrHPV+). The number of reads is specified for each sample. The SNPs position are specified by the red arrow.
Figure 2.
Figure 2.
Average of methylated, unmethylated and partially methylated reads in HPV positive (HPV+) and negative (HPV-) of penile squamous cell carcinoma. Positive samples were considered as p16INK4a+ or hrHPV+.
Figure 3.
Figure 3.
Percentage of methylation for each CpG site in HPV positive (HPV+) and negative (HPV-) of penile squamous cell carcinoma. The CTCF binding site is indicated by the grey arrow. Positive samples were considered as p16INK4a+ or hrHPV+.
Figure 4.
Figure 4.
Kaplan – Meier curve for survival probability (n = 27). (a) methylation levels; (b) rs2107425 genotype; (c) s2071094 genotype.
See this image and copyright information in PMC

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