dc.contributor.advisor |
Bohlander, S |
en |
dc.contributor.author |
Sung, Yih Jian |
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dc.date.accessioned |
2018-07-18T21:56:31Z |
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dc.date.issued |
2018 |
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dc.identifier.uri |
http://hdl.handle.net/2292/37505 |
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dc.description |
Full text is available to authenticated members of The University of Auckland only. |
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dc.description.abstract |
Cancers are genetic diseases that affect millions of people worldwide and are one of the major causes of premature death. Cancers result from the dysregulated proliferation of cells and their invasion into other tissue. Carcinogenesis requires multiple co-operating genetic alterations, which cause the dysregulation of normal cellular processes and can sometimes be targeted in therapies. Structural genetic alterations such as those resulting from balanced translocations are especially prevalent in leukaemia, a cancer of the blood. The fusion gene resulting from the t(10;11)(p12;q14) translocation found in human leukaemia is the CALM/AF10 which has been shown to drive leukaemogenesis in murine models. A CALM/AF10 transgenic zebrafish model was created in which CALM/AF10 is expressed in zebrafish haematopoietic stem cells. Some CALM/AF10 zebrafish developed disease symptoms after 3 to 4 months which were compatible with the assumptions that they had developed leukaemia. We carried out histological analysis of kidney tissue from CALM/AF10 zebrafish to understand the nature and extent of the disease. We found massive infiltration of the kidney with cells that crowded out the normal kidney cells, suggesting infiltration of the kidneys with leukaemic cells. As it is known that cancer, and also leukaemia, is a multistep genetic process, we employed whole exome sequencing to search for additional, co-operating mutations in these zebrafish leukaemic cells. We identified somatic mutations in kras, ezh1, and dnmt3bb.2, the human homologues of which are associated with cancer or are closely related to genes that are associated with cancer. This work provides a starting point for future experiments that investigate the genetic causes of leukaemia in CALM/AF10 transgenic zebrafish. |
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dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
Masters Thesis - University of Auckland |
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dc.relation.isreferencedby |
UoA99265072008802091 |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
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dc.rights |
Restricted Item. Available to authenticated members of The University of Auckland. |
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dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
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dc.title |
Whole exome sequencing of zebrafish CALM/AF10-initiated haematopoietic tumours |
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dc.type |
Thesis |
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thesis.degree.discipline |
Biomedical Sciences |
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thesis.degree.grantor |
The University of Auckland |
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thesis.degree.level |
Masters |
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dc.rights.holder |
Copyright: The author |
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pubs.elements-id |
748022 |
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pubs.record-created-at-source-date |
2018-07-19 |
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dc.identifier.wikidata |
Q112938356 |
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