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Access Type
WSU Access
Date of Award
January 2022
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Molecular Biology and Genetics
First Advisor
Michael A. Tainsky
Abstract
Patients with familial cancer patterns frequently test negative for known pathogenic germline mutations in cancer risk genes. To address this missing link in the diagnosis of hereditary cancer syndromes and to improve the quality and accuracy of cancer genetic testing, a number of variants of unknown significance in the known risk genes ATM and BRCA2 were selected after presenting in a cohort of ovarian cancer patients with likely hereditary cancer syndromes but no genetic diagnosis. In vitro functional assays were carried out on all the variants, and provide consistent and definitive data indicating loss of function in several of these variants. These may be responsible for the missing heritability seen in this cohort, and widespread application of this method could be useful in addressing the low sensitivity of current genetic testing panels.
Recommended Citation
Baughan, Scott Lawrence, "In Depth Analysis Of Variants Of Unknown Significance From A High Risk Cohort Identifies Likely Pathogenic Missense Mutations" (2022). Wayne State University Dissertations. 3730.
https://digitalcommons.wayne.edu/oa_dissertations/3730