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

House Dust Mite Related Allergic Rhinitis and REM Sleep Disturbances

PURPOSE: Sleep disturbances are common in patients with allergic rhinitis (AR). Perennial allergens like house dust mites (HDM) are difficult to avoid and have nocturnal impacts on the respiratory system and Quality of Life (QOL). The Rapid Eye Movement (REM) sleep stage is associated with memory, cognition, dreams, and overall restfulness, which can be impaired in AR patients with Sleep Disordered Breathing (SDB) even when normal all-night apnea-hypopnea (AHI) or respiratory disturbance (RDI) indices are noted on polysomnography (PSG). We hypothesized that AR HDM allergen positive patients would show REM-specific SDB reflected in their objectively elevated REM-RDI values. MATERIALS AND METHODS: This retrospective analysis of 100 patients included 47 with HDM positive allergy testing. All patients underwent PSG testing calculating the RDI during REM. Multivariate logistic regression models evaluated relationships between allergic statuses and sleep parameters while controlling for potential confounders. RESULTS: Compared with allergy negative patients, HDM allergen positive patients were significantly more likely (OR 4.29, 95%CI 1.26-14.62) to have a REM-RDI in the moderate/severe range (≥15 events/h). CONCLUSIONS: Our study highlighted the significance of respiratory allergies to HDM in patients with SDB. We revealed a significant relationship between HDM allergen positivity and SDB characterized by elevated REM-RDI regardless of all-night AHI, RDI, or REM-AHI values. Clinical implications of knowing about disturbed REM and/or HDM allergenicity include better preparation, treatment, outcomes, and QOL for allergic, SDB, and upper airway surgery patients

Arcade Sutures to Minimize Ear Displacement in Rhytidectomy

Ear deformities after rhytidectomy are not uncommon and have a significant impact on cosmetic success. We postulate the use of horizontal mattress suspension sutures in the anterior face anchored to the deep temporalis fascia (DTF) during rhytidectomy allows for a vertical lift while minimizing the risk to the frontal branch of the facial nerve and decreasing forward rotation of the ear. To compare auricular displacement during rhytidectomy using an arcade of horizontal mattress suspension sutures anchored to the DTF instead of the preauricular pre-parotid fascia, and evaluate outcomes with this modification at 1 year. This was a proof of concept prospective cohort study of 20 patients (40 sides) undergoing rhytidectomy by a single plastic surgeon (level of evidence 4). Intraoperative measurements were taken to determine the amount of auricular displacement with suspension sutures placed in the preauricular fascia compared with the DTF. To confirm longevity, we compared ear position preoperatively and at 1 year after rhytidectomy with our technique. There was significantly less auricular displacement when superficial musculoaponeurotic system (SMAS) suspension sutures were placed in the DTF 0.75 ± 0.69 mm compared with the preauricular fascia 9.71 ± 2.57 mm ( \u3c 0.00001). With our technique at an average follow-up of 370.3 days, there was no significant change in auricular rotation compared with preoperative photos ( = 0.125).Our simple rhytidectomy modification allows for vertical resuspension of the SMAS in the anterior face in a safe manner while minimizing displacement of the auricle

Prosthetics in Facial Reconstruction

Reconstruction of the head and neck can be a challenging undertaking owing to numerous considerations for successful rehabilitation. Although head and neck defects were once considered irretrievably morbid and associated with a poor quality of life, advances in surgical technique has immensely contributed to the well-being of these patients. However, all patients are not suitable surgical candidates and many have sought nonsurgical options for functional and cosmetic restoration. As such, the advent of prostheses has ameliorated those concerns and provided a viable alternative for select patient populations. Prosthetic reconstruction has evolved significantly over the past decade. Advances in biocompatible materials and imaging adjuncts have spurred further discovery and forward progress. A multidisciplinary approach to head and neck reconstruction focused on appropriate expectations and patient-centered goals is most successfully coordinated by a team of head and neck surgeons, maxillofacial surgeons, and prosthetic specialists. The aim of this article is to provide a comprehensive review of the current trends for prosthetic rehabilitation of head and neck defects, and further elaborate on the limitations and advancements in the field

Syphilis of the oropharynx: Case series of The Great Masquerader

OBJECTIVE: Syphilis is a sexually transmitted infection with various presentations. Although, oropharyngeal manifestations are known to occur, the purpose of this study is to present the first case series in which the lesions were initially mistaken for human-papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A multi-institutional retrospective review. RESULTS: Six cases of oropharyngeal syphilis were initially thought to be secondary to OPSCC due to presentation. Symptoms were vague and exam findings consisted of either a tonsillar or base of tongue mass, or lymphadenopathy. Biopsies were negative for OPSCC. Further workup diagnosed syphilis, with resolution of symptoms and lesions after antibiotic treatment. CONCLUSIONS: Head and neck manifestations of syphilis have been reported in the literature. However, this is the first series reporting on oropharyngeal syphilis masquerading as HPV-related OPSCC. Ultimately, otolaryngologists must maintain a high suspicion for syphilis in order to ensure prompt diagnosis and treatment

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.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.Peer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: 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