A Review of the Repair of DNA Double Strand Breaks in the Development of Oral Cancer.

Prime, Stephen S, Darski, Piotr, Hunter, Keith D ORCID: 0000-0002-7873-0877, Cirillo, Nicola and Parkinson, E Kenneth (2024) A Review of the Repair of DNA Double Strand Breaks in the Development of Oral Cancer. International journal of molecular sciences, 25 (7). p. 4092.

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Official URL: http://dx.doi.org/10.3390/ijms25074092

Abstract

We explore the possibility that defects in genes associated with the response and repair of DNA double strand breaks predispose oral potentially malignant disorders (OPMD) to undergo malignant transformation to oral squamous cell carcinoma (OSCC). Defects in the homologous recombination/Fanconi anemia (HR/FA), but not in the non-homologous end joining, causes the DNA repair pathway to appear to be consistent with features of familial conditions that are predisposed to OSCC (FA, Bloom's syndrome, Ataxia Telangiectasia); this is true for OSCC that occurs in young patients, sometimes with little/no exposure to classical risk factors. Even in Dyskeratosis Congenita, a disorder of the telomerase complex that is also predisposed to OSCC, attempts at maintaining telomere length involve a pathway with shared HR genes. Defects in the HR/FA pathway therefore appear to be pivotal in conditions that are predisposed to OSCC. There is also some evidence that abnormalities in the HR/FA pathway are associated with malignant transformation of sporadic cases OPMD and OSCC. We provide data showing overexpression of HR/FA genes in a cell-cycle-dependent manner in a series of OPMD-derived immortal keratinocyte cell lines compared to their mortal counterparts. The observations in this study argue strongly for an important role of the HA/FA DNA repair pathway in the development of OSCC.

Item Type:	Article
Uncontrolled Keywords:	Humans, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Mouth Neoplasms, Fanconi Anemia, DNA, Squamous Cell Carcinoma of Head and Neck
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	17 Apr 2024 10:09
Last Modified:	01 May 2024 00:13
DOI:	10.3390/ijms25074092
Open Access URL:	https://www.mdpi.com/1422-0067/25/7/4092/review_re...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3180404