SummaryAccurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.
Given the success of targeted agents in specific populations it is expected that some degree of molecular biomarker testing will become standard of care for many, if not all, cancers. To facilitate this, cancer centers worldwide are experimenting with targeted "panel" sequencing of selected mutations. Recent advances in genomic technology enable the generation of genome-scale data sets for individual patients. Recognizing the risk, inherent in panel sequencing, of failing to detect meaningful somatic alterations, we sought to establish processes to integrate data from wholegenome analysis (WGA) into routine cancer care. Between June 2012 and August 2014, 100 adult patients with incurable cancers consented to participate in the Personalized OncoGenomics (POG) study. Fresh tumor and blood samples were obtained and used for whole-genome and RNA sequencing. Computational approaches were used to identify candidate driver mutations, genes, and pathways. Diagnostic and drug information were then sought based on these candidate "drivers." Reports were generated and discussed weekly in a multidisciplinary team setting. Other multidisciplinary working groups were assembled to establish guidelines on the interpretation, communication, and integration of individual genomic findings into patient care. Of 78 patients for whom WGA was possible, results were considered actionable in 55 cases. In 23 of these 55 cases, the patients received treatments motivated by WGA. Our experience indicates that a multidisciplinary team of clinicians and scientists can implement a paradigm in which WGA is integrated into the care of late stage cancer patients to inform systemic therapy decisions.
Breast cancer screening programs operate across Canada providing mammography to women in target age groups with the goal of reducing breast cancer mortality through early detection of tumors. Disparities in breast screening participation among socio‐demographic groups, including immigrants, have been reported in Canada. Our objectives were to: (1) assess breast screening participation and retention among immigrant and nonimmigrant women in British Columbia (BC), Canada; and (2) to characterize factors associated with screening among screening‐age recent immigrant women in BC. We examined 2 population‐based cohorts of women eligible for breast screening participation (537 783 women) and retention (281 052 women) using linked health and immigration data. Breast screening rates were presented according to socio‐demographic and health‐related variables stratified by birth country. Factors associated with screening among recent immigrant women were explored using Poisson regression. We observed marked variation in screening participation across birth country cohorts. Eastern European/Central Asian women showed low participation (37.9%) with rates from individual countries ranging from 35.0% to 49.0%. Participation rates for immigrant women from the most common birth countries, such as China/Macau/Hong Kong/Taiwan (45.7%), India (44.5%), the Philippines (45.9%), and South Korea (39.0%), were lower than the nonimmigrant rates (51.2%). Retention rates showed less variation by birth country; however, some disparities between immigrant and nonimmigrant groups persisted. Associations between screening indicators and study factors varied considerably across immigrant groups. Primary care physician visits were consistently positively associated with screening participation; this variable was also the only predictor associated with screening within each of the groups of recent immigrants. Our study provides unique data on both screening participation and retention among Canadian immigrant women compiled by individual country of birth. Our results are further demonstration that screening disparities exist among immigrant populations as well as in comparison with nonimmigrant women.
Rationale and Aim As medical schools reduce the hours of anatomy teaching, residents in anatomy-intensive residency programs like radiology must independently acquire the anatomy knowledge needed to achieve competency. The purpose of this study was to develop and evaluate a 4-week competency-based self-directed anatomy rotation for junior residents. Methods Seven post-graduate year 1 (PGY-1) radiology residents completed a 4-week rotation of radiologic anatomy. The objectives were developed from standards, senior residents, and expert opinion, and the competency-based curriculum included self-directed modules. Pre-course and post-course tests were administered and test scores were compared using an unpaired t test. In addition, PGY-1 residents completed a course evaluation and survey regarding their anatomy knowledge and anatomy exposure prior to completing the course. Results Out of the 25 points available, the average pre-test score was 10.79 ± 2.78 (range 8–16.5), and the average post-test score was 21.64 ± 2.23 (range 18.5–25). This difference was statistically significant ( P < .0001). The PGY-1 residents reported receiving < 10% of dedicated radiologic anatomy teaching prior to residency and felt unprepared for the anatomy required in residency. Overall, residents felt more confident in looking at images after completing the self-directed radiologic anatomy course. Conclusion This study demonstrates the feasibility of creating a self-directed course for radiology residents that significant improves their anatomy knowledge. Given the trend in medical undergraduate education away from dedicated anatomy teaching, residency programs should consider addressing anatomy education more formally for junior residents to ensure that trainees receive the foundational knowledge required for residency.
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