DNA Methylation Profiling as a Tool for Testicular Germ Cell Tumors Subtyping

Abstract

Aim: Assess differential patterns of selected five genes’ promoter methylation among testicular germ cell tumors (TGCT) subtypes. Materials & methods: CRIPTO, HOXA9, MGMT, RASSF1A and SCGB3A1 promoter methylation levels were evaluated by quantitative methylation-specific PCR in 161 TGCT and 16 controls. Associations between clinicopathological parameters and promoter methylation levels were assessed, and receiver operating characteristics curve analysis was performed. Results: Promoter methylation of CRIPTO/HOXA9/SCGB3A1 panel and RASSF1A best discriminated between controls and nonseminomatous tumors or seminomas, respectively, whereas HOXA9/RASSF1A panel displayed the best discriminative performance between nonseminomatous tumor and seminomas. Significant differences in CRIPTO, MGMT and RASSF1A methylation levels were depicted between pure forms and matched mixed components of seminomas and embryonal carcinoma. HOXA9, RASSF1A and SCGB3A1 promoter methylation significantly associated with tumor stage. Conclusion: Different combinations of five genes’ promoter methylation levels discriminate among TGCT subtypes. Methylation patterns may also assist in identification of more clinically aggressive tumors.

Keywords::

• CRIPTO
• DNA methylation biomarkers
• HOXA9
• MGMT
• prognosis
• RASSF1A
• SCGB3A1
• testicular germ cell tumors

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2217/epi-2018-0034

Financial & competing interests disclosure

This study was funded by research grants from Research Center of Portuguese Oncology Institute of Porto (FB-GEBC-27 and 19-CI-IPOP-2016) and by Fundação para a Ciência e Tecnologia (POCI-01-0145-FEDER-29043). J Lobo is supported by a PhD fellowship from FCT-Fundação para a Ciência e Tecnologia (SFRH/BD/132751/2017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was conducted after approval by institutional ethics review board of Portuguese Oncology Institute of Porto, Portugal (Comissão de Ética para a Saúde – CES-IPO-12-017).

Additional information

Funding

This study was funded by research grants from Research Center of Portuguese Oncology Institute of Porto (FB-GEBC-27 and 19-CI-IPOP-2016) and by Fundação para a Ciência e Tecnologia (POCI-01-0145-FEDER-29043). J Lobo is supported by a PhD fellowship from FCT-Fundação para a Ciência e Tecnologia (SFRH/BD/132751/2017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.