Identification of a class of human cancer germline genes with transcriptional silencing refractory to the hypomethylating drug 5-aza-2ˈ-deoxycytidine

Ahmed Almatrafi, Julia Feichtinger, Ellen G. Vernon, Natalia Gomez Escobar, Jane A. Wakeman, Lee D. Larcombe, Ramsey J. McFarlane*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    Abstract



    Bona fide germline genes have expression restricted to the germ cells of the gonads. Testis-specific germline development-associated genes can become activated in cancer cells and can potentially drive the oncogenic process and serve as therapeutic/biomarker targets; such germline genes are referred to as cancer/testis genes. Many cancer/testis genes are silenced via hypermethylation of CpG islands in their associated transcriptional control regions and become activated upon treatment with DNA hypomethylating agents; such hypomethylation-induced activation of cancer/testis genes provides a potential combination approach to augment immunotherapeutics. Thus, understanding cancer/testis gene regulation is of increasing clinical importance. Previously studied cancer/testis gene activation has focused on X chromosome encoded cancer/testis genes. Here we find that a sub-set of non-X encoded cancer/testis genes are silenced in non-germline cells via a mechanism that is refractory to epigenetic dysregulation, including treatment with the hypomethylating agent 5-aza-2ˈ-deoxycytidine and the histone deacetylase inhibitor tricostatin A. These findings formally indicate that there is a sub-group of the clinically important cancer/testis genes that are unlikely to be activated in clinical therapeutic approaches using hypomethylating agents and it indicates a unique transcriptional silencing mechanism for germline genes in non-germline cells that might provide a target mechanism for new clinical therapies
    Original languageEnglish
    Pages (from-to)745-750
    JournalOncoscience
    Volume1
    Issue number11
    DOIs
    Publication statusPublished - 2014

    Fields of Expertise

    • Human- & Biotechnology

    Treatment code (Nähere Zuordnung)

    • Basic - Fundamental (Grundlagenforschung)
    • Experimental

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