Clonal fitness inferred from time-series modelling of single-cell cancer genomes.

Progress in defining genomic fitness landscapes in cancer, especially those defined by copy number alterations (CNAs), has been impeded by lack of time-series single-cell sampling of polyclonal populations and temporal statistical models1-7. Here we generated 42,000 genomes from multi-year time-series single-cell whole-genome sequencing of breast epithelium and primary triple-negative breast cancer (TNBC) patient-derived xenografts (PDXs), revealing the nature of CNA-defined clonal fitness dynamics induced by TP53 mutation and cisplatin chemotherapy. Using a new Wright-Fisher population genetics model8,9 to infer clonal fitness, we found that TP53 mutation alters the fitness landscape, reproducibly distributing fitness over a larger number of clones associated with distinct CNAs. Furthermore, in TNBC PDX models with mutated TP53, inferred fitness coefficients from CNA-based genotypes accurately forecast experimentally enforced clonal competition dynamics. Drug treatment in three long-term serially passaged TNBC PDXs resulted in cisplatin-resistant clones emerging from low-fitness phylogenetic lineages in the untreated setting. Conversely, high-fitness clones from treatment-naive controls were eradicated, signalling an inversion of the fitness landscape. Finally, upon release of drug, selection pressure dynamics were reversed, indicating a fitness cost of treatment resistance. Together, our findings define clonal fitness linked to both CNA and therapeutic resistance in polyclonal tumours.

Inaugural Pan-Canadian RADGames: Results From a Successful Approach to Radiology Education for Medical Students.

RATIONALE AND OBJECTIVES: A goal in radiology undergraduate medical education is to improve exposure to the field. In 2022, the Canadian Association of Radiologists' Medical Student Network hosted for the first time "RADGames," an interactive image interpretation contest for medical students across Canada. This program was aimed to spark interest in radiology and improve students' image interpretation skills through gamification with expert guidance. MATERIALS AND METHODS: Volunteers from Radiology Interest Groups in Canadian medical schools set up a virtual event for the competition using breakout rooms and a quiz platform. Participant recruitment was through social media and advertisement by medical student associations. Participants were surveyed anonymously for feedback following the event. Data about previous exposure to and knowledge of radiology, and an evaluation of the event including self-perceived impact on participants' understanding of the field were collected. RESULTS: Eighty seven medical students from 15 of Canada's 17 medical schools competed against one another virtually. Forty seven (54%) responded to the post-event evaluation survey. All responses about the event itself were favourable. Respondents overwhelmingly indicated that RADGames increased their interest in radiology (38, 81%), their understanding of the work of a radiologist (31, 66%) and their knowledge about medical imaging (46, 98%), and improved their confidence in basic imaging interpretation (36, 77%). CONCLUSION: The Canadian Association of Radiologists' Medical Student Network hosted Canada's first national image interpretation competition for medical students, RADGames. Feedback was overwhelmingly positive, with perceived benefits to participants on their understanding of and interest in radiology.