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CLOCK GENES AS TUMOR MARKERS IN COLORRECTAL CANCER

D. Fajardo Puig1 , J.J. Retuerta Vilariño2 , P. Cano Barquilla3 , V. Jiménez Ortega3 , P. Fernández Mateos3 , A.I. Esquifino Parras3 , F.J. Martínez Picabea2 , D. Bolado López de Andújar4

1 Departamento de Bioquímica y Biología Molecular (UCM) y Hospital Universi- tario 12 de Octubre. 2 Departamento de Bioquímica y Biología Molecular (UCM). 3 Departamento de Bioquímica y Biología Molecular (UCM) y Hospital Clínico San Carlos (IdISSC). 4 Hospital Universitario 12 de Octubre.Madrid. Spain

Objectives: Colorectal cancer is the third leading cause of death associated with neoplastic processes. Currently, we know that the genetic regulation of genes that regulate cell division is highly influenced by the so-called biological clock genes, which, when deregulated, lead to uncontrolled division that can trigger this type of carcinogenesis. The current work aims to clarify which clock genes are those that are most related to this type of pathology and how it can be used as markers that predict its evolution.

Methods: In order to carry out this work, an exhaustive bibliographic investi- gation has been done in PubMed and more than 20 different articles have been analysed.

Results: In colorectal adenoma, elevations of the clock genes are not usually seen and only mutations appear in the Clock gene with a frequency of 10%. In the case of colorectal carcinoma, it is observed that between 27% and 47% of the patients present mutations in the Clock, Per1, Per2, Cry1 and Cry2 genes. The elevation of the Per1, Per2 and Clock genes is related to a larger tumour size (> 50mm, p <0.05 in all 3 cases) but only Per2 and Clock are directly related to a greater degree of invasiveness and tumour progression.

Tumours that have mutations in Per2 that raise their expression are usually low survival tumours because this gene is an apoptotic inducer. The elevation of the Cry1 and Cry2 genes is related to a higher rate of cell division because it decreases the transcription of the Wee1 gene, which does not phosphorylate cyclin-B and CDK1, preventing blockage in the G2 / M phase of the cell cycle, which, under normal conditions,Wee1 gene, stops.

Conclusion Clock genes can give information on how a colorectal cancer will evolve, since tumours with mutations in Clock, Per1 and Per2 are more invasive and larger, while those with mutations in Cry1 and Cry2 have low cells survival and faster cell division.

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