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Genes 2017, 8(2), 45; doi:10.3390/genes8020045

Links between DNA Replication, Stem Cells and Cancer

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bldg. 6A, Room 3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA
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Academic Editor: Eishi Noguchi
Received: 20 November 2016 / Revised: 2 January 2017 / Accepted: 12 January 2017 / Published: 25 January 2017
(This article belongs to the Special Issue DNA Replication Controls)
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Abstract

Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in early embryos give rise to all of the cell lineages in the embryo and adult, but when they mislocate to ectopic sites, they produce tumors. Remarkably, pluripotent stem cells, like many cancer cells, depend on the Geminin protein to prevent excess DNA replication from triggering DNA damage-dependent apoptosis. This link between the control of DNA replication during early development and germ cell neoplasia reveals Geminin as a potential chemotherapeutic target in the eradication of cancer progenitor cells. View Full-Text
Keywords: DNA re-replication; endoreplication; mitotic slippage; Geminin; teratoma; teratocarcinoma; embryonic stem cells; embryonal carcinoma cells; cancer stem cells; germ cell neoplasia DNA re-replication; endoreplication; mitotic slippage; Geminin; teratoma; teratocarcinoma; embryonic stem cells; embryonal carcinoma cells; cancer stem cells; germ cell neoplasia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Vassilev, A.; DePamphilis, M.L. Links between DNA Replication, Stem Cells and Cancer. Genes 2017, 8, 45.

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