Oncotarget

Research Papers:

Overexpression of Rad51C splice variants in colorectal tumors

Arjun Kalvala, Li Gao, Brittany Aguila, Tyler Reese, Gregory A. Otterson, Miguel A. Villalona-Calero _ and Wenrui Duan

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Oncotarget. 2015; 6:8777-8787. https://doi.org/10.18632/oncotarget.3209

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Abstract

Arjun Kalvala1, Li Gao1, Brittany Aguila1, Tyler Reese1, Gregory A. Otterson1,2, Miguel A. Villalona-Calero1,2,3 and Wenrui Duan1,2

1 Comprehensive Cancer Center, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, U.S.A

2 Division of Medical Oncology Department of Internal Medicine, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, U.S.A

3 Department of Pharmacology at The Ohio State University College of Medicine and Public Health, Columbus, Ohio, U.S.A

Correspondence:

Miguel A. Villalona-Calero, email:

Wenrui Duan, email:

Keywords: Rad51C isoform overexpression, Promoter methylation, Colorectal tumors

Received: July 29, 2014 Accepted: December 24, 2014 Published: December 30, 2014

Abstract

Functional alterations in Rad51C are the cause of the Fanconi anemia complementation group O (FANCO) gene disorder. We have identified novel splice variants of Rad51C mRNA in colorectal tumors and cells. The alternatively spliced transcript variants are formed either without exon-7 (variant 1), without exon 6 and 7 (variant 2) or without exon 7 and 8 (variant 3).

Real time PCR analysis of nine pair-matched colorectal tumors and non-tumors showed that variant 1 was overexpressed in tumors compared to matched non-tumors. Among 38 colorectal tumor RNA samples analyzed, 18 contained variant 1, 12 contained variant 2, 14 contained variant 3, and eight expressed full length Rad51C exclusively. Bisulfite DNA sequencing showed promoter methylation of Rad51C in tumor cells. 5-azacytidine treatment of LS-174T cells caused a 14 fold increase in variant 1, a 4.8 fold increase for variant 3 and 3.4 fold for variant 2 compared to 2.5 fold increase in WT.

Expression of Rad51C variants is associated with FANCD2 foci positive colorectal tumors and is associated with microsatellite stability in those tumors. Further investigation is needed to elucidate differential function of the Rad51C variants to evaluate potential effects in drug resistance and DNA repair.


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