Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
[eng] I have used the brain tumours that originate in Drosophila larvae upon depletion of the brain tumor (brat) gene as a model to study neoplastic malignant growth. I have used genetic analysis to interrogate the Drosophila genome for genes that can be targeted to inhibit the development or arrest...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/191601 |
| Acceso en línea: | https://hdl.handle.net/2445/191601 http://hdl.handle.net/10803/687262 |
| Access Level: | acceso abierto |
| Palabra clave: | Oncologia Tumors Drosòfila melanogaster Divisió cel·lular Oncology Drosophila melanogaster Cell division |
| Sumario: | [eng] I have used the brain tumours that originate in Drosophila larvae upon depletion of the brain tumor (brat) gene as a model to study neoplastic malignant growth. I have used genetic analysis to interrogate the Drosophila genome for genes that can be targeted to inhibit the development or arrest the growth of brat tumours. The targetable genome identified through this functional genomics approach includes 80 suppressors of brat tumour growth (brat-SPRs). I have also carried out transcriptomic analysis of brat tumours through which I have been able to define a brat tumour signature that includes 625 and 903 genes that are significantly up- and down-regulated in brat larval brain tumours compared to normal larval brains. From the combined analysis of my functional genomics and transcriptomics data I have concluded that correlation between the extent of gene expression dysregulation and function with regards to tumour development is so low that the former is not a good predictor of the latter. From the combined analysis of my own data on brat tumours and published functional genomics and transcriptomics data on the brain tumours that originate upon depletion of lethal(3)malignant brain tumor (l(3)mbt), henceforth referred to as mbt tumours, I have found that nearly 60% (47/80) of the brat-SPRs are tumour-type specific in the sense that they do not suppress mbt tumours. One of the non-tumour specific suppressors (i.e. mbt&brat-SPRs) identified in my study is Vacuolar protein sorting 26 (Vps26). Vps26 had been reported to be a type II neuroblast lineage-specific tumour suppressor. My results show that in addition, Vps26 function contributes to brat tumour growth and is essential for long-term survival of mbt tumours. My results also suggest that unlike its published tumour suppressor function, Vps26 mbt&brat-SPR activity might be independent of its role in the retromer complex. |
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