Cancer mouse models, include genetically engineered mouse (GEM) models and xenografts (PDX) are popular systems for studying human cancers in research and clinical laboratories.
One essential question for using any model is to determine what degree the model faithfully represents the human counterparts, especially on the mutational level. Analyses of mouse somatic mutations pose a unique challenge due to the diverse genetic background in GEM and mouse stromal contamination in PDX models.
We overcame these challenges using specifically designed computational approaches. The identified mutations in mice re-capitulate human cancer hotspot mutations:
Selected papers
Wei L, Murphy BL, Wu G, Parker M, Easton J, Gilbertson RJ, Zhang J, Roussel MF. Exome sequencing analysis of murine medulloblastoma models identifies WDR11 as a potential tumor suppressor in Group 3 tumors. Oncotarget. 2017 Jul 27;8(39):64685-64697. doi: 10.18632/oncotarget.19642. PMID: 29029386; PMCID: PMC5630286.
Wei L, Chintala S, Ciamporcero E, Ramakrishnan S, Elbanna M, Wang J, Hu Q, Glenn ST, Murakami M, Liu L, Gomez EC, Sun Y, Conroy J, Miles KM, Malathi K, Ramaiah S, Anbarasu A, Woloszynska-Read A, Johnson CS, Conroy J, Liu S, Morrison CD, Pili R. Genomic profiling is predictive of response to cisplatin treatment but not to PI3K inhibition in bladder cancer patient-derived xenografts. Oncotarget. 2016 Nov 22;7(47):76374-76389. doi: 10.18632/oncotarget.13062. PMID: 27823983; PMCID: PMC5363516.
Dang J, Wei L, de Ridder J, Su X, Rust AG, Roberts KG, Payne-Turner D, Cheng J, Ma J, Qu C, Wu G, Song G, Huether RG, Schulman B, Janke L, Zhang J, Downing JR, van der Weyden L, Adams DJ, Mullighan CG. PAX5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia. Blood. 2015 Jun 4;125(23):3609-17. doi: 10.1182/blood-2015-02-626127. Epub 2015 Apr 8. PMID: 25855603; PMCID: PMC4458800.