PDF(Pubmed)
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.
摘要：
阴茎鳞状细胞癌（SCC）是一种罕见的侵袭性肿瘤，主要与生活方式和人乳头瘤病毒（HPV）感染有关。H19差异甲基化区域（H19DMR）的环境诱导的印记丢失（LOI）与肿瘤发生的早期事件中的许多癌症有关，并且可能与阴茎SCC的发病机理有关。我们试图通过亚硫酸氢盐测序（bis-seq）评估H19DMR的DNA甲基化模式及其与阴茎SCC男性中HPV感染的关联。我们观察到阴茎SCC的H19DMR的平均甲基化为32.2％±11.6％，并且没有观察到p16INK4a（p=0.59）和高危HPV（p=0.338）标志物与甲基化水平之间的关联。根据p16INK4a+或hrHPV+的HPV阳性(35.4%±10%)和两个标志物的阴性(32.4%±10.1%)组,平均甲基化没有变化。由于所分析的区域具有CTCF蛋白的结合位点，周围CpG位点的低甲基化可能会改变其绝缘体功能。此外,H19DMR时多形核细胞浸润与低甲基化呈正相关(p=0.035)。这里,我们报道,无论HPV感染如何,阴茎SCC中H19DMR的低甲基化可能导致肿瘤进展和侵袭性.
