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dc.contributor.advisorGanem, Neil J.en_US
dc.contributor.authorDiDomizio, Amandaen_US
dc.date.accessioned2020-06-05T18:25:48Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/2144/41133
dc.description.abstractWhole genome doubling (WGD) generates genetically unstable tetraploid cells that fuel tumorigenesis. Cells that undergo WGD must acquire adaptive characteristics to accommodate their tetraploid state, and these adaptations may confer unique vulnerabilities that can be exploited therapeutically. We analyzed the genomes of ~9,700 primary human cancer samples to uncover genetic alterations that are specifically enriched in WGD+ cancer cells. Through integrating our genetic analysis with gene essentiality data acquired from Project Achilles, we identified gene dependencies in WGD+ cells. Moreover, we identified genes that are essential for the viability of WGD+ cancer cells, but non-essential to non-transformed diploid cells. We demonstrated that the gene encoding for the mitotic kinesin KIF18A is dispensable for mitosis in diploid cells, but becomes critical for accurate chromosome segregation and viability in WGD+ cells, making it an attractive drug target. Collectively, this work revealed new strategies to specifically target WGD+ cancer cells, namely targeting the gene KIF18A, while sparing the normal diploid cells from which they arise.en_US
dc.language.isoen_US
dc.subjectPharmacologyen_US
dc.subjectCanceren_US
dc.subjectCRISPR screenen_US
dc.subjectKIF18Aen_US
dc.subjectPloidy-specific lethal genesen_US
dc.subjectWhole genome doublingen_US
dc.titleWhole genome doubling confers unique genetic vulnerabilities on tumor cellsen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2020-06-04T22:07:34Z
dc.description.embargo2022-06-04T00:00:00Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-2303-1585


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