A model of early steps in genetically complex cancer types has been developed using overexpression of the Drosophila gene Dmel\Myc in combination with loss-of-function for Dmel\p53. See also the human disease model reports 'cancer, multiple, TP53-related' (FBhh0000340) and 'cancer, multiple, MYC-related' (FBhh0000402).
Although the orthologous human genes, Hsap\TP53 and Hsap\MYC, have been introduced into flies, they have not been used in the context of this disease model.
For this TP53-MYC-related cancer model, specific targeting of transgene expression to the anterior/posterior boundary of the wing disc allows sensitive visual assays of transformation. This system has been used to test the additional modification of candidate genes located within copy number alterations commonly observed in triple-negative breast cancer (TNBC). Each candidate gene was tested in the p53 mutant, Myc overexpression background: amplified genes were assessed by overexpression of the Drosophila ortholog; deleted genes were assessed by RNAi-mediated knockdown or by removing one functional copy of the Drosophila ortholog. Six of the positive '3-hit' models were subsequently assessed for response to a chemotherapeutic drug; in all cases, increased genetic complexity reduced treatment response.
[updated Sep. 2024 by FlyBase; FBrf0222196]
Many to one: 3 human to 1 Drosophila; additional orthologous human genes are TP63 and TP73.
Many to one: 3 human to 1 Drosophila; additional (lower-scoring) human orthologs are MYCN and MYCL.
Orthologous to human gene MYC (reciprocal best hit); lower scoring ortholog of human MYCN and MYCL (1 Drosophila to 3 human).
High-scoring ortholog of human genes TP53, TP63 and TP73 (1 Drosophila to many human).