BACKGROUND: 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. OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS AND DISCUSSION: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS AND DISCUSSION: 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. CONCLUSIONS: 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.
Authors: Timothy M Pierpont; Amy M Lyndaker; Claire M Anderson; Qiming Jin; Elizabeth S Moore; Jamie L Roden; Alicia Braxton; Lina Bagepalli; Nandita Kataria; Hilary Zhaoxu Hu; Jason Garness; Matthew S Cook; Blanche Capel; Donald H Schlafer; Teresa Southard; Robert S Weiss Journal: Cell Rep Date: 2017-11-14 Impact factor: 9.423
Authors: Kristian Almstrup; Christina E Hoei-Hansen; Ute Wirkner; Jonathon Blake; Christian Schwager; Wilhelm Ansorge; John E Nielsen; Niels E Skakkebaek; Ewa Rajpert-De Meyts; Henrik Leffers Journal: Cancer Res Date: 2004-07-15 Impact factor: 12.701
Authors: J Bartkova; Z Horejsí; M Sehested; J M Nesland; E Rajpert-De Meyts; N E Skakkebaek; M Stucki; S Jackson; J Lukas; J Bartek Journal: Oncogene Date: 2007-06-04 Impact factor: 9.867
Authors: Hui Shen; Juliann Shih; Daniel P Hollern; Linghua Wang; Reanne Bowlby; Satish K Tickoo; Vésteinn Thorsson; Andrew J Mungall; Yulia Newton; Apurva M Hegde; Joshua Armenia; Francisco Sánchez-Vega; John Pluta; Louise C Pyle; Rohit Mehra; Victor E Reuter; Guilherme Godoy; Jeffrey Jones; Carl S Shelley; Darren R Feldman; Daniel O Vidal; Davor Lessel; Tomislav Kulis; Flavio M Cárcano; Kristen M Leraas; Tara M Lichtenberg; Denise Brooks; Andrew D Cherniack; Juok Cho; David I Heiman; Katayoon Kasaian; Minwei Liu; Michael S Noble; Liu Xi; Hailei Zhang; Wanding Zhou; Jean C ZenKlusen; Carolyn M Hutter; Ina Felau; Jiashan Zhang; Nikolaus Schultz; Gad Getz; Matthew Meyerson; Joshua M Stuart; Rehan Akbani; David A Wheeler; Peter W Laird; Katherine L Nathanson; Victoria K Cortessis; Katherine A Hoadley Journal: Cell Rep Date: 2018-06-12 Impact factor: 9.423
Authors: Amanda R Loehr; Timothy M Pierpont; Eric Gelsleichter; Anabella Maria D Galang; Irma R Fernandez; Elizabeth S Moore; Matthew Z Guo; Andrew D Miller; Robert S Weiss Journal: Cancers (Basel) Date: 2021-04-23 Impact factor: 6.639
Authors: Dennis M Timmerman; Thomas F Eleveld; Ad J M Gillis; Carlijn C Friedrichs; Sanne Hillenius; Tessa L Remmers; Sruthi Sriram; Leendert H J Looijenga Journal: Int J Mol Sci Date: 2021-10-29 Impact factor: 5.923
Authors: Roberta Bergero; Peter Ellis; Wilfried Haerty; Lee Larcombe; Iain Macaulay; Tarang Mehta; Mette Mogensen; David Murray; Will Nash; Matthew J Neale; Rebecca O'Connor; Christian Ottolini; Ned Peel; Luke Ramsey; Ben Skinner; Alexander Suh; Michael Summers; Yu Sun; Alison Tidy; Raheleh Rahbari; Claudia Rathje; Simone Immler Journal: Biol Rev Camb Philos Soc Date: 2021-01-01