DNA methylation profiling as a tool for testicular germ cell tumors subtyping

Epigenomics. 2018 Dec;10(12):1511-1523. doi: 10.2217/epi-2018-0034. Epub 2018 Nov 12.

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: DNA methylation biomarkers; prognosis; testicular germ cell tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cytokines / genetics
  • DNA Methylation*
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • GPI-Linked Proteins / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasms, Germ Cell and Embryonal / classification*
  • Neoplasms, Germ Cell and Embryonal / diagnosis
  • Neoplasms, Germ Cell and Embryonal / genetics
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Portugal
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • ROC Curve
  • Testicular Neoplasms / classification*
  • Testicular Neoplasms / diagnosis
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / pathology
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • Cytokines
  • GPI-Linked Proteins
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • RASSF1 protein, human
  • SCGB3A1 protein, human
  • TDGF1 protein, human
  • Tumor Suppressor Proteins
  • homeobox protein HOXA9
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes

Supplementary concepts

  • Testicular Germ Cell Tumor