Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Global Health Education in Pathology Residency

Abstract Objectives Pathology and laboratory medicine (PALM) services in low- and middle-income countries are essential to combat the increasing prevalence of cancer in addition to providing documentation of cancer types and trends for future allocation of public health resources. There are many ways PALM as a whole can engage on the global health front. This study summarizes the efforts and results of a global health educational and clinical elective for pathology residents in Quetzaltenango, Guatemala. Methods Pathology residents led and implemented the project, working alongside an in-country pathologist and project collaborator to instill project sustainability and allow for future capacity building. Results An educational elective was established between the pathology departments of the University of Virginia and Hospital Regional de Occidente in Quetzaltenango, Guatemala. Two residents at a time engaged in a month-long educational elective assisting and learning from the in-country pathologist in anatomic pathology clinical work. Conclusions The project is an example of a global health initiative centering on the enhancement of PALM services in a low-resource environment via a bidirectional, sustainable educational exchange. </jats:sec