Research Papers: Chromosome:
Potential biomarkers of DNA replication stress in cancer
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Liqun Ren1, Long Chen1, Wei Wu2, Lorenza Garribba2, Huanna Tian1, Zihui Liu3, Ivan Vogel2, Chunhui Li3, Ian D. Hickson2,4 and Ying Liu2
1 Basic Medical Research Institute, Chengde Medical University, Chengde, China
2 Center for Chromosome Stability, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
3 Pathology Department, Affiliated Hospital, Chengde Medical University, Chengde, China
4 Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
Ying Liu, email:
Keywords: cancer biomarker, chromosome instability, common fragile sites, MiDAS, replication stress, Chromosome Section
Received: March 08, 2017 Accepted: March 28, 2017 Published: April 07, 2017
Oncogene activation is an established driver of tumorigenesis. An apparently inevitable consequence of oncogene activation is the generation of DNA replication stress (RS), a feature common to most cancer cells. RS, in turn, is a causal factor in the development of chromosome instability (CIN), a near universal feature of solid tumors. It is likely that CIN and RS are mutually reinforcing drivers that not only accelerate tumorigenesis, but also permit cancer cells to adapt to diverse and hostile environments. This article reviews the genetic changes present in cancer cells that influence oncogene-induced RS and CIN, with a particular emphasis on regions of the human genome that show enhanced sensitivity to the destabilizing effects of RS, such as common fragile sites. Because RS exists in a wide range of cancer types, we propose that the proteins involved counteracting this stress are potential biomarkers for indicating the degree of RS in cancer specimens. To test this hypothesis, we conducted a pilot study to validate whether some of proteins that are known from in vitro studies to play an essential role in the RS pathway could be suitable as a biomarker. Our results indicated that this is possible. With this review and pilot study, we aim to accelerate the development of a biomarker for analysis of RS in tumor biopsy specimens, which could ultimately help to stratify patients for different forms of therapy such as the RS inhibitors already undergoing clinical trials.
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