Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/6798
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dc.contributor.advisorRutter, Jareden_US
dc.contributor.authorYADAV, TARUNen_US
dc.date.accessioned2022-05-06T05:19:28Z-
dc.date.available2022-05-06T05:19:28Z-
dc.date.issued2022-05-
dc.identifier.citation81en_US
dc.identifier.urihttp://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/6798-
dc.description.abstractPTEN deletion is a universal mechanism through which a cancer cell inactivates PTEN activity in order to achieve the ability to proliferate excessively. These PTEN deletions are often accompanied by a deletion of the adjacent gene ATAD1 which has critical roles to play in the maintenance of mitochondrial protein homeostasis. The vulnerabilities imposed by these PTEN / ATAD1 co- deletions on a cancer cell can be exploited in the treatment of aggressive malignancies such as T-cell Acute Lymphoblastic Leukemia (T-ALL). In this thesis, I carried out an in- depth analysis of publicly available datasets in order to determine the genomic landscape of PTEN and ATAD1. My analyses showed that PTEN inactivating alterations are common in T-ALL and close to 10 % of T-ALL cases harbor a PTEN gene deletion. I was also able to confirm that over 33 % of PTEN deletion events are accompanied by the concomitant deletion of ATAD1 in these T-ALL samples. Further, PTEN mutations are frequent in over 14 % of T-ALL cases and these often target the PTEN C2 domain that is critical for the proliferation- suppressing activity of PTEN. Importantly, in line with ATAD1’s essential role in mitochondrial homeostasis and cell survival, the ATAD1 gene does not harbor any inactivating mutations suggesting that it is not a tumor suppressor gene (TSG). Taken together, my analyses confirmed the occurrence of PTEN / ATAD1 co-deletions in T-ALL and strongly substantiate the clinical advantages that targeting such modalities can offer for the treatment of cancers that are not responsive to traditional therapeutics.en_US
dc.description.sponsorshipKVPY Fellowship, Infosys Foundationen_US
dc.language.isoenen_US
dc.subjectPTENen_US
dc.subjectATAD1en_US
dc.subjectPassenger deletionsen_US
dc.subjectT-ALLen_US
dc.subjectCopy Number Alterationsen_US
dc.subjectSynthetic lethalityen_US
dc.subjectCanceren_US
dc.titleAn Analysis of the Genomic Landscape of PTEN and ATAD1 in T-cell Acute Lymphoblastic Leukemiaen_US
dc.typeThesisen_US
dc.type.degreeBS-MSen_US
dc.contributor.departmentDept. of Biologyen_US
dc.contributor.registration20171058en_US
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