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

"Why haven't you taken any pain killers?" A patient focused study of the walking wounded in an urban emergency department

Objectives: (1) To assess the proportion of patients of triage category 3–5 presenting to the minor side of an urban emergency department who present without taking prior pain relief, and (2) to describe the reasons why they do not take pain relief for their presenting complaint Method: By patient interview of a convenience sample of 60 adult patients in the setting of an urban emergency department. Results: Fifteen of 60 patients had taken analgesia and 45 of 60 (75%) had not. Sixteen reasons were volunteered to the interviewer. Most patients offered one reason only 39 of 45 (87%). The three commonest single reasons cited for not taking pain relief were "don't like taking tablets" 10 (22%), "run out of tablets" 10 (22%), five (11%) said their "pain not bad enough". Six (13%) patients cited two reasons for not taking pain relief. Only three (6%) patients indicated that they "did not think about pain relief". Six (13%) of patients had inappropriate perceptions of how pain killers may interfere with their care. Conclusion: Most patients presenting with painful conditions to the minor side of an urban emergency department had not taken pain relief. The study highlights there are many different reasons for this and staff should not presume that it was because the patient "did not think about it". Ongoing education of staff and patients is needed