Thesis
Utilizing large genomic datasets to evaluate novel, rare variants in ribonucleoside-diphosphate reductase subunit M2 B
Master of Science (M.S.), Drexel University
2018
DOI:
https://doi.org/10.17918/1h6z-b931
Abstract
Despite many inherited cancer cases being associated with alterations in DNA repair-associated genes, a significant number of such cancer cases remain genetically unidentified. One of the most frequently altered genes in cancer is Tp53 which codes for the p53 protein and has been widely studied. A transcriptional target of p53, is RRM2B. The RRM2B protein (also known as p53R2) plays a crucial role in DNA replication and repair by replenishing the dNTP pool in cells. Alterations in RRM2B have been associated with RRM2B-related mitochondrial DNA depletion syndrome but its role in cancer is not fully understood. Due to its relevance as a DNA replication and repair related protein and being a target of p53, we wanted to investigate potential relevance of germline variants of this gene to cancer. We investigated, using a bioinformatics tool (Annovar) and large-scale genomic database (ExAC), the burden of germline RRM2B variants present in the general population as well as identify potential cancer relevant variants. We also compared the germline data with tumor alterations obtained from TCGA and COSMIC databases. Relevant variants were then mapped on to the protein structure of RRM2B and visualized for analysis using PyMol. Through this analysis, two novel germline variants N157S and I280V, were identified. These have not been previously characterized, were predicted to be pathogenic by multiple variant prediction tools and were found to be present only in the germline of individuals with cancer (TCGA-ExAC). These variants have also been reported in stomach adenocarcinoma and cutaneous melanoma (from TCGA).
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Details
- Title
- Utilizing large genomic datasets to evaluate novel, rare variants in ribonucleoside-diphosphate reductase subunit M2 B
- Creators
- Waleed Iqbal - DU
- Contributors
- Erica Golemis (Advisor) - Drexel University (1970-)Sanjeevani Arora (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- 65 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 8853; 991014632158504721