Hypermethylation of Genes in Testicular Embryonal Carcinomas

Overview

Journal Br J Cancer

Specialty Oncology

Date 2015 Dec 2

PMID 26625006

Citations 14

Authors

Hoi-Hung Cheung

Yanzhou Yang

Tin-Lap Lee

Owen Rennert

Wai-Yee Chan

Affiliations

Soon will be listed here.

Abstract

Background: Testicular embryonal carcinoma (EC) is a major subtype of non-seminomatous germ cell tumours in males. Embryonal carcinomas are pluripotent, undifferentiated germ cell tumours believed to originate from primordial germ cells. Epigenetic changes during testicular EC tumorigenesis require better elucidation.

Methods: To identify epigenetic changes during testicular neoplastic transformation, we profiled DNA methylation of six ECs. These samples represent different stages (stage I and stage III) of divergent invasiveness. Non-cancerous testicular tissues were included. Expression of a number of hypermethylated genes were examined by quantitative RT-PCR and immunohistochemistry (IHC).

Results: A total of 1167 tumour-hypermethylated differentially methylated regions (DMRs) were identified across the genome. Among them, 40 genes/ncRNAs were found to have hypermethylated promoters. Quantitative RT-PCR confirmed downregulation of 8 out of 9 of the genes. Among the confirmed genes, five were sex-linked genes, including X-linked genes STAG2, SPANXD/E and MIR1184, and Y-linked genes RBMY1A1/1B/1D and FAM197Y2P. RBMY1A is a testis-specific gene for spermatogenesis. RNF168 and USP13 are potential tumour suppressors. Expression of RBMY1A was lost in EC and seminoma as documented in the Protein Atlas. We confirmed downregulation of USP13 in EC by IHC.

Conclusions: Our genome-wide analysis of testicular EC identified methylation changes in several previously unknown genes. This may provide insight of crosstalk between normal germ cell development and carcinogenesis.

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