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World J Gastroenterol. Sep 21, 2014; 20(35): 12522-12525
Published online Sep 21, 2014. doi: 10.3748/wjg.v20.i35.12522
Mitotic crossover - an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma
Branislav Rovcanin, Ivan Ivanovski, Olivera Djuric, Dimitrije Nikolic, Jelena Petrovic, Petar Ivanovski
Branislav Rovcanin, Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
Ivan Ivanovski, Institute for Mother and Child Health Care, Faculty of Medicine, University of Belgrade, Belgrade 11070, Serbia
Olivera Djuric, Institute for Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
Dimitrije Nikolic, Petar Ivanovski, University Children’s Hospital, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
Jelena Petrovic, Faculty of Medicine, University of Belgrade, Belgrade 11070, Serbia
Author contributions: Each author indicated gave substantial contributions to the conception and design of the article, acquisition of data, drafting of the article, critical revision for important intellectual content, and final approval of the version to be published.
Supported by The Ministry of Science and Education (partially), Republic of Serbia, No. 175091
Correspondence to: Petar Ivanovski, MD, PhD, Professor of Pediatrics, University Children’s Hospital, Faculty of Medicine, University of Belgrade, Tirsova 10, Belgrade 11000, Serbia. ivanovsk@eunet.rs
Telephone: +381-11-2060666 Fax: +381-11-2684672
Received: February 23, 2014
Revised: April 22, 2014
Accepted: May 19, 2014
Published online: September 21, 2014
Processing time: 207 Days and 21.5 Hours
Abstract

Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors.

Keywords: Mitotic crossing over; Loss of heterozygosity; Carcinogenesis; Inhibitors; Colorectal carcinoma; Cancer chemoprevention

Core tip: We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, and its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors.