How cell-to-cell copy number alterations that underpin genomic instability1 in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer2, remains understudied. Here, by applying scaled single-cell whole-genome sequencing3 to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct ‘foreground’ mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences. In TNBC and HGSC, clone-specific high-level amplifications in known oncogenes were highly prevalent in tumours bearing fold-back inversions, relative to tumours with homologous recombination deficiency, and were associated with increased clone-to-clone phenotypic variation. Parallel haplotype-specific alterations were also commonly observed, leading to phylogenetic evolutionary diversity and clone-specific mono-allelic expression. Serrate variants were increased in tumours with fold-back inversions and were highly correlated with increased genomic diversity of cellular populations. Together, our findings show that cell-to-cell structural variation contributes to the origins of phenotypic and evolutionary diversity in TNBC and HGSC, and provide insight into the genomic and mutational states of individual cancer cells.

Purpose This paper aims to review the latest management developments across the globe and pinpoint practical implications from cutting-edge research and case studies. Design/methodology/approach This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context. Findings Organizational development strategies must be carefully considered before they are enacted, based on involvement, the issue at hand, the existing structures of the firm, and managerial structures. Originality/value The briefing saves busy executives, strategists and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.

Mental health concerns are highly prevalent among university populations, often overwhelming available clinical services. Mobile health (mHealth) interventions can offer low-cost care to large populations without requiring in-person treatment, making mHealth an excellent candidate for addressing unmet needs. MindTrails is an existing online intervention that uses Cognitive Bias Modification for Interpretations (CBM-I) to change anxious thinking patterns. We describe the co-design of Hoos Think Calmly, a mobile adaptation of MindTrails tailored specifically to undergraduate and graduate students, faculty, and staff in a university setting. The aim of this study was to explore the preferences, experiences, and opinions of university members to inform the design and implementation of Hoos Think Calmly. We conducted semi-structured interviews with N=24 leaders of diverse student groups, staff who work closely with university populations, and potential users (i.e., students, faculty, and staff) and identified themes with a template analysis. University members valued a personalized, credible, and gamified mHealth intervention that is non-time-intensive and accessible to diverse populations. This study identifies key features university community members value in mHealth and builds on previous work demonstrating the importance of including stakeholders in mHealth development.