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

Forum : Vol. 36, No. 03 (Fall : 2012)

https://digitalcommons.usf.edu/forum_magazine/1018/thumbnail.jp

Narcolepsy with cataplexy associated with nocturnal compulsive behaviors: a case-control study

STUDY OBJECTIVES: To assess the prevalence of sleep related-eating disorder (SRED) and nocturnal smoking (NS) in patients with narcolepsy with cataplexy (NC). DESIGN: Case-control study. SETTING: University hospital. PATIENTS OR PARTICIPANTS: 65 consecutive adult NC patients (33 men; mean age 43.9 \ub1 19.2 years) and 65 age-, sex-, and geographical origin-matched controls. INTERVENTIONS: Validated questionnaires were used to investigate SRED, NS, restless legs syndrome (RLS), and psychopathological traits (using Eating Disorder Inventory-2 [EDI-2]; Maudsley Obsessive-Compulsive Inventory [MOCI]; and Beck Depression Inventory [BDI]). MEASUREMENTS AND RESULTS: NC patients showed a higher prevalence of SRED (32% vs 3%, P=0.00001), NS (21% vs 0%, P=0.00006), and RLS (18% vs 5%, P=0.013) than controls. Moreover, NC patients presented more frequently with an eating-related pathological profile on the EDI-2 (80% vs 46%, P=0.00006) and had a higher prevalence of depressed mood on the BDI (41% vs 18%, P=0.004). In comparison to patients without SRED, NC patients with SRED were more frequently women (71% vs 39%, P=0.013), had higher "bulimic" (29% vs 2%, P=0.004) and "social insecurity" (48% vs 18%, P=0.013) traits on the EDI-2, had higher obsessive-compulsiveness on the MOCI (29% vs 4%, P = 0.009), and were more depressed on the BDI (67% vs 29%, P=0.005). NC patients with NS showed more frequent pathological profiles on the EDI-2 (100% vs 75%, P=0.035), including the "bulimic" (29% vs 6%, P=0.015), "perfectionism" (43% vs 14%, P=0.016), and "social insecurity" (50% vs 22, P=0.035) profiles. CONCLUSION: Our study shows a strong association of the compulsive nocturnal behaviors SRED and NS with adult NC