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PMID: 31119900 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Germline genome protection: implications for gamete quality and germ cell tumorigenesis.

Andrology ·Vol. 7 ·No. 4 ·2019-00-00 ·Pages 516-526

Bloom JC, Loehr AR, Schimenti JC, Weiss RS

Abstract

Germ cells have a unique and critical role as the conduit for hereditary information and therefore employ multiple strategies to protect genomic integrity and avoid mutations. Unlike somatic cells, which often respond to DNA damage by arresting the cell cycle and conducting DNA repair, germ cells as well as long-lived pluripotent stem cells typically avoid the use of error-prone repair mechanisms and favor apoptosis, reducing the risk of genetic alterations. Testicular germ cell tumors, the most common cancers of young men, arise from pre-natal germ cells. To summarize the current understanding of DNA damage response mechanisms in pre-meiotic germ cells and to discuss how they impact both the origins of testicular germ cell tumors and their remarkable responsiveness to genotoxic chemotherapy. We conducted a review of literature gathered from PubMed regarding the DNA damage response properties of testicular germ cell tumors and the germ cells from which they arise, as well as the influence of these mechanisms on therapeutic responses by testicular germ cell tumors. This review provides a comprehensive evaluation of how the developmental origins of male germ cells and their inherent germ cell-like DNA damage response directly impact the development and therapeutic sensitivity of testicular germ cell tumors. The DNA damage response of germ cells directly impacts the development and therapeutic sensitivity of testicular germ cell tumors. Recent advances in the study of primordial germ cells, post-natal mitotically dividing germ cells, and pluripotent stem cells will allow for new investigations into the initiation, progression, and treatment of testicular germ cell tumors.

Keywords
DNA damage response DNA repair apoptosis chemoresistance chemosensitivity germ cell testicular germ cell tumor
MeSH Terms
Animals DNA Damage Drug Resistance, Neoplasm Embryonic Germ Cells/physiology Humans Neoplasms, Germ Cell and Embryonal/drug therapy,etiology Testicular Neoplasms/drug therapy,etiology
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bloom J C ORCID
Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
Loehr A R
Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
Schimenti J C
Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
Weiss R S ORCID
Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
Supplementary Concepts
Testicular Germ Cell Tumor (Disease)
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Article Info
Journal
Andrology
Abbr.
Andrology
ISSN
2047-2927
DOI
10.1111/andr.12651
Published
2019-00-00
Epub
2019-00-22
Pages
516-526
Language
English
Region
England
NLM ID
101585129
PMCID
PMC6635098
Subset
IM
Grants
NCI NIH HHS · R21 CA185256 · United States
NIH HHS · R21 CA185256 · United States
NICHD NIH HHS · T32 HD057854 · United States
NYSTEM · C026421 · International
External Links
PubMed source DOI: 10.1111/andr.12651 PMC Full Text View journal details
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