THE BULK OF CANCER ASSOCIATED MUTATION

THE BULK OF CANCER ASSOCIATED MUTATION

 

THE BULK OF CANCER ASSOCIATED MUTATIONS IN A CRC FAMILY ARE NOVEL SOMATIC EVENTS AND LIKELY A PRODUCT OF APOBEC3B MUTAGENESIS

Authors and affiliations

Omnia E. Yousif1, Rayan Saifeldin Yousif1, Ali  Sultan,  Suleiman H. Suleiman2, *Muntasir E. Ibrahim1

*Corresponding author: Muntasir E. Ibrahim

1.Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum. P.O. Box 102, Sudan,2.Soba University Hospital, Department of Surgery, Faculty of Medicine, University of Khartoum, Sudan,3. Weill Cornell Medical College in Qatar, Qatar

Abstract

Aim

To investigate the role of APOBEC-3B gene in familial colorectal cancer

Background

Colorectal cancer is the third most common cancer worldwide. The disease may occur due to mutations in undiscovered genetic loci in patients with no Lynch. Hitherto, new technologies like next generation sequencing (NGS) provide a persuasive tool and deciphered a wide range of culprits that contributed to tumorigenesis process. Different spheres were described as causative factors of the disease including genetic, epigenetic and infection. In this regard APOBEC family of editing proteins plays a major role in causing non-random mutations. However, much to be learned about the interaction between: APOBEC family, novel mutations and Epstein–Barr virus (EBV).

Methods

 Herein, multidisciplinary approach (NGS, qRT-PCR, in situ hyperdization and microarray) was use in order to investigate different mutations in one CRC family (2 cancer and three normal controls).

Results

 Using NGS we identified 3845/44886 (9%), 3575/43186 (8.3%) novel variants among tumor samples in compared to 1795/43832(4%), 1759/44241 (4%), 1813/44967 (4%) in control sample (p=0.0001). Among the novel variants, variant with significant score in (SIFT and PolyPhen) tools were (317/1759 (18%), 353/1795 (20%) in tumor samples and 217/1795 (12%), 202/1759 (11%) and 52/1813(3%) in control samples (p=0.0001). Pathway analysis of the significant score genes reported The Chromobox family gene (Cbx), DNA-repair proteins (XRCC) genes families. Intriguingly, APOBEC family (APOBEC4, APOBEC3H and APOBEC3A) were predicted to be mutated. Results of PCR and in situ hyperdization of (EBV) virus showed faint signal. Interestingly, quantitative PCR (qRT-PCR) analysis of APOBEC3B show 6 fold increases in the CRC tissue in compare with matched normal controls.

Conclusions

In conclusion, we proposed that APOBEC family may affect the detected somatic novel mutation and lead to cancer.  Knowledge of APOBECs mutagenesis in cancer may yield significant diagnostic, prognostic value and new therapeutic opportunities. 

 

 Name

Omnia Elfatih yousif

Title

PhD, molecular biology

Affiliations of presenter

Researcher, federal ministry of health

 

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