Rad51C-ATXN7 fusion gene expression in colorectal tumors.
Fusion proteins have unique oncogenic properties and their identification can be useful either as diagnostic or therapeutic targets. Next generation sequencing data have previously shown a fusion gene formed between Rad51C and ATXN7 genes in the MCF7 breast cancer cell line. However, the existence of this fusion gene in colorectal patient tumor tissues is largely still unknown.



We evaluated for the presence of Rad51C-ATXN7 fusion gene in colorectal tumors and cells by RT-PCR, PCR, Topo TA cloning, Real time PCR, immunoprecipitation and immunoblotting techniques.



We identified two forms of fusion mRNAs between Rad51C and ATXN7 in the colorectal tumors, including a Variant 1 (fusion transcript between Rad51C exons 1-7 and ATXN7 exons 6-13), and a Variant 2 (between Rad51C exons 1-6 and ATXN7 exons 6-13). In silico analysis showed that the Variant 1 produces a truncated protein, whereas the Variant 2 was predicted to produce a fusion protein with molecular weight of 110 KDa. Immunoprecipitation and Western blot analysis further showed a 110 KDa protein in colorectal tumors. 5-Azacytidine treatment of LS-174 T cells caused a 3.51-fold increase in expression of the fusion gene (Variant 2) as compared to no treatment controls evaluated by real time PCR.



In conclusion we found a fusion gene between DNA repair gene Rad51C and neuro-cerebral ataxia Ataxin-7 gene in colorectal tumors. The in-frame fusion transcript of Variant 2 results in a fusion protein with molecular weight of 110 KDa. In addition, we found that expression of fusion gene is associated with functional impairment of Fanconi Anemia (FA) DNA repair pathway in colorectal tumors. The expression of Rad51C-ATXN7 in tumors warrants further investigation, as it suggests the potential of the fusion gene in treatment and predictive value in colorectal cancers.
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Arjun
A
Kalvala
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Li
L
Gao
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Brittany
B
Aguila
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Kathleen
K
Dotts
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Mohammad
M
Rahman
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.|Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Serge P
SP
Nana-Sinkam
Department of Pathology, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Xiaoping
X
Zhou
Department of Radiology, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Qi-En
QE
Wang
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.|Division of Medical Oncology Department of Internal Medicine, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Joseph
J
Amann
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.|Division of Medical Oncology Department of Internal Medicine, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA.
Gregory A
GA
Otterson
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA. miguel.villalona@osumc.edu.|Division of Medical Oncology Department of Internal Medicine, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA. miguel.villalona@osumc.edu.|Department of Pharmacology, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA. miguel.villalona@osumc.edu.
Miguel A
MA
Villalona-Calero
Comprehensive Cancer Center, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA. wenrui.duan@osumc.edu.|Division of Medical Oncology Department of Internal Medicine, the Ohio State University College of Medicine and Public Health, Columbus, Ohio, 43210, USA. wenrui.duan@osumc.edu.
Wenrui
W
Duan
D000067719:Ataxin-7 / Q000235:genetics* / Q000378:metabolism; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D003001:Cloning, Molecular / Q000379:methods*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D003198:Computer Simulation; D019175:DNA Methylation / Q000187:drug effects; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D014644:Genetic Variation; D006801:Humans; D008970:Molecular Weight; D015514:Oncogene Proteins, Fusion / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; C448305:RAD51C protein, human; D001374:Azacitidine
ATXN7; Chromosomal translocation; Colorectal tumors; Fusion gene; Rad51C