Pediatrics Commons^™

Examining How Children's Gender Influences Parents’ Perceptions Of The Local Environment And Their Influence On Children's Independent Mobility, Alina Medeiros, Andrew F. Clark, Gina Martin, Jamie A. Seabrook, Jason Gilliland

Paediatrics Publications

Physical inactivity among children is a public health concern. Children's ability to travel independently is associated with increased physical activity and social connectedness. Consequently, it is concerning that children's independent mobility has decreased in recent years. Studies have highlighted that rates of independent mobility vary by gender; this study analyzed how correlates of independent mobility vary between boys (n = 476) and girls (n = 618) attending 32 elementary schools in Southwestern Ontario. Hierarchical logistic regression modeling methods were used. All analyzes were stratified by gender. For boys, age was negatively associated with travel with peers. Having one or more …

Correlates Of Lifetime And Past Month Vape Use In A Sample Of Canadian University Students, Jamie A. Seabrook, Jasna Twynstra, Jason A. Gilliland

Paediatrics Publications

Introduction: This study examines correlates of lifetime (ie, ever vaped) and past month vape use among students aged 17 to 19 years, 20 to 25 years, and 26+ years from Western University in London, Ontario. The secondary objective is to assess lifetime and past month vape use among students not of legal age to purchase vaping products in Ontario (ie, those 17 to 18 years only). Methods: Using Qualtrics, a cross-sectional survey was sent via email to all students at Western University (N = 38 442), assessing their current and past risk-taking behaviors, mental health, sociodemographic characteristics, as well as …

The Quantity And Composition Of Household Food Waste During The Covid-19 Pandemic: A Direct Measurement Study In Canada, Haley Everitt, Paul Van Der Werf, Jamie A. Seabrook, Alexander Wray, Jason A. Gilliland

Paediatrics Publications

The COVID-19 pandemic may have amplified the environmental, social, and economic implications of household food waste. A better understanding of household food wasting during the pandemic is needed to improve the management of waste and develop best practices for municipal waste management programs under crisis circumstances. A waste composition study was undertaken with 100 single-family households across the city of London, Ontario, Canada to determine the quantity and composition of household food waste disposed in June 2020, during the first wave of the COVID-19 pandemic. This study examines how household demographic, socioeconomic, and neighbourhood food environment characteristics influence household food …

Examining How Changes In Provincial Policy On Vape Marketing Impacted The Distribution Of Vaping Advertisements Near Secondary Schools In London, Ontario, Gina Martin, Drew D. Bowman, Megan Graat, Andrew F. Clark, Alexander J. Wray, Zoe Askwith, Jamie A. Seabrook, Jason A. Gilliland

Paediatrics Publications

Objectives: On January 1, 2020, the Government of Ontario passed a regulation banning vaping advertisements by retailers, apart from specialty shops. A motivation for this ban was to limit youth exposure to vaping advertisements. The primary goal of this research was to evaluate the impact of this ban on the number and density of vaping advertisements surrounding secondary schools. Additionally, we examined whether the number of vaping advertisements varied by school socio-demographic characteristics. Methods: This study used a pre-post design. Audits were conducted December 2019 (pre-ban) and again January to February 2020 (post-ban), to identify vaping advertisements within 800 m …

Sensitivity Of Arterial Spin Labeling For Characterization Of Longitudinal Perfusion Changes In Frontotemporal Dementia And Related Disorders, Tracy Ssali, Udunna C. Anazodo, Lucas Narciso, Linshan Liu, Sarah Jesso, Lauryn Richardson, Matthias Günther, Simon Konstandin, Klaus Eickel, Frank Prato, Elizabeth Finger, Keith St. Lawrence

Paediatrics Publications

Background: Advances in the understanding of the pathophysiology of frontotemporal dementia (FTD) and related disorders, along with the development of novel candidate disease modifying treatments, have stimulated the need for tools to assess the efficacy of new therapies. While perfusion imaging by arterial spin labeling (ASL) is an attractive approach for longitudinal imaging biomarkers of neurodegeneration, sources of variability between sessions including arterial transit times (ATT) and fluctuations in resting perfusion can reduce its sensitivity. Establishing the magnitude of perfusion changes that can be reliably detected is necessary to delineate longitudinal perfusion changes related to disease processes from the effects …

In Utero Exposure To ∆9-Tetrahydrocannabinol Leads To Postnatal Catch-Up Growth And Dysmetabolism In The Adult Rat Liver, Daniel Hardy, Shelby Oke, Kendrick Lee, Rosemary Papp, Steven Laviolette

Data and Test Instruments

No abstract provided.

Exercise In Pregnancy Increases Placental Angiogenin Without Changes In Oxidative Or Endoplasmic Reticulum Stress, Daniel Hardy, Xin Mu, Katelyn Marchiori, Michelle Mottola

Data and Test Instruments

No abstract provided.

Transcriptional Profiling Of Leukocytes In Critically Ill Covid19 Patients: Implications For Interferon Response And Coagulation, Sean E Gill, Claudia C Dos Santos, David B O'Gorman, David E Carter, Eric K Patterson, Marat Slessarev, Claudio Martin, Mark Daley, Michael R. Miller, Gediminas Cepinskas, Douglas Fraser

Paediatrics Publications

BACKGROUND: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and …

Automated Office Blood Pressure Measurement For The Diagnosis Of Hypertension, Guido Filler, Maria E Díaz-González De Ferris

Paediatrics Publications

Editorial

Parental Psychosocial Aspects And Stressors Involved In The Management Of Inborn Errors Of Metabolism., Prashanth Rajasekar, Srinitya Gannavarapu, Melanie Napier, Asuri N Prasad, Akshya Vasudev, Andrew Mantulak, Beth K Potter, Chitra Prasad

Paediatrics Publications

Parents of children with inborn errors of metabolism (IEM) face numerous psychosocial challenges. An increased understanding and awareness of these stressors can ensure better overall outcomes for the entire family. We conducted semi-structured, in-person interviews with ten parents to identify psychosocial stressors, strategies, and supports they utilized to overcome their challenges. Our interview guide was designed to elicit familial experiences during the pre- and post-diagnosis periods. The themes and sub-themes were identified through qualitative descriptive textual analysis of audio-recorded transcripts. Major themes identified include ambiguity of illness, changing family and spousal dynamics, and navigating the healthcare system. Sub-themes revolved around …

Survival Benefit For Individuals With Constitutional Mismatch Repair Deficiency Syndrome And Brain Tumors Who Undergo Surveillance Protocol. A Report From The International Replication Repair Consortium, Ayse Bahar Ercan, Carol Durno, Vanessa J. Bianchi, Melissa Edwards, Melyssa Aronson, Eric Bouffet, Abeer Al-Battashi, Musa Alharbi, Donald Basel, Elizabeth Cairney

Paediatrics Publications

BACKGROUND

Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome resulting in early onset central nervous system (CNS) and other cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol. METHODS

We surveyed all confirmed CMMRD patients in the International Replication Repair Deficiency Consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging (CNS and total body MRI) studies were employed. Survival analyses and efficacy of each method were assessed. RESULTS

Surveillance data were collected from 105 CMMRD individuals from 41 countries. Of the 193 malignant tumors, CNS malignancies …

Frameshift Mutations At The C-Terminus Of Hist1h1e Result In A Specific Dna Hypomethylation Signature, A. Ciolfi, E. Aref-Eshghi, S. Pizzi, L. Pedace, E. Miele, J. Kerkhof, E. Flex, S. Martinelli, F.C. Radio, C.A.L Ruivenkamp, G.W.E. Santen, E.K. Bijlsma, D.Q.C.M. Barge-Schaapveld, K. Ounap, V. Mok Siu, F. F. Kooy, B. Dallapiccola, B. Sadikovic, M. Tartaglia

Paediatrics Publications

No abstract provided.

Isolated Sulfite Oxidase Deficiency: A Founder Mutation., Aizeddin A Mhanni, Cheryl R Greenberg, Elizabeth L Spriggs, Ronald Agatep, Reena Ray Sisk, Chitra Prasad

Paediatrics Publications

Isolated sulfite oxidase deficiency is a rare autosomal recessive inborn error of sulfur metabolism. Clinical features generally include devastating neurologic dysfunction, ectopia lentis, and increased urinary excretion of sulfite, thiosulfate, and

Five-Month-Old Male With Chronic Diarrhea., Hailey C Barootes, Erin R Peebles, Dhandapani Ashok, Suzanne Ratko, Andrea C Yu

Paediatrics Publications

No abstract provided.

Lactate Preconditioning Promotes A Hif-1Α-Mediated Metabolic Shift From Oxphos To Glycolysis In Normal Human Diploid Fibroblasts, Alexandra M. Kozlov, Asad Lone, Dean H. Betts, Robert C. Cumming

Paediatrics Publications

Recent evidence has emerged that cancer cells can use various metabolites as fuel sources. Restricting cultured cancer cells to sole metabolite fuel sources can promote metabolic changes leading to enhanced glycolysis or mitochondrial OXPHOS. However, the efect of metabolite-restriction on non-transformed cells remains largely unexplored. Here we examined the efect of restricting media fuel sources, including glucose, pyruvate or lactate, on the metabolic state of cultured human dermal fbroblasts. Fibroblasts cultured in lactate-only medium exhibited reduced PDH phosphorylation, indicative of OXPHOS, and a concurrent elevation of ROS. Lactate exposure primed fbroblasts to switch to glycolysis by increasing transcript abundance of …

Machine Learning Identifies Clinical And Genetic Factors Associated With Anthracycline Cardiotoxicity In Pediatric Cancer Survivors, Marie-A Chaix, Neha Parmar, Caroline Kinnear, Myriam Lafreniere-Roula,, Oyediran Akinrinade, Roderick Yao, Anastasia Miron, Emily Lam, Guoliang Meng, Anne Christie, Ashok Kumar Manickaraj, Stacey Marjerrison, Rejane Dillenburg, Mylène Bassal, Jane Lougheed, Shayna Zelcer, Herschel Rosenberg, David Hodgson, Leonard Sender, Paul Kantor, Cedric Manlhiot, James Ellis, Luc Mertens, Paul C. Nathan, Seema Mital

Paediatrics Publications

BACKGROUND Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. OBJECTIVES This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. METHODS We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (<= 250 mg/m(2)), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin >250 mg/m(2) were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in …

Hyoscine Butylbromide Versus Acetaminophen For Nonspecific Colicky Abdominal Pain In Children: A Randomized Controlled Trial., Naveen Poonai, Kriti Kumar, Kamary Coriolano, Graham Thompson, Shaily Brahmbhatt, Emily Dzongowski, Holly Stevens, Priti Gupta, Michael Miller, Sharlene Elsie, Dhandapani Ashok, Gary Joubert, Rod Lim, Andreana Bütter, Samina Ali

Paediatrics Publications

BACKGROUND: Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain.

METHODS: We randomly allocated children aged 8-17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 …

Drug Therapy During Pregnancy., Dongmei Sun, Janine R. Hutson, Facundo Garcia-Bournissen Md Phd

Paediatrics Publications

No abstract provided.

A Live-Online Mindfulness-Based Intervention For Children Living With Epilepsy And Their Families: Protocol For A Randomized Controlled Trial Of Making Mindfulness Matter©., Klajdi Puka, Karen Bax, Andrea Andrade, Margo Devries-Rizzo, Hema Gangam, Simon Levin, Maryam N Nouri, Asuri N Prasad, Mary Secco, Guangyong Zou, Kathy N Speechley

Paediatrics Publications

BACKGROUND: Epilepsy extends far beyond seizures; up to 80% of children with epilepsy (CWE) may have comorbid cognitive or mental health problems, and up to 50% of parents of CWE are at risk for major depression. Past research has also shown that family environment has a greater influence on children's and parents' health-related quality of life (HRQOL) and mental health than epilepsy-related factors. There is a pressing need for low-cost, innovative interventions to improve HRQOL and mental health for CWE and their parents. The aim of this randomized controlled trial (RCT) is to evaluate whether an interactive online mindfulness-based intervention …

Tp63-Mutation As A Cause Of Prenatal Lethal Multicystic Dysplastic Kidneys, Isabel Friedmann, Carla Campagnolo, Nancy Chan, Ghislain Hardy, Maha Saleh

Paediatrics Publications

BACKGROUND: Ectrodactyly-ectodermal dysplasia-clefting syndrome 3 (EEC) is one of the six overlapping syndromes caused by mutations in the tumor protein p63 gene (TP63). EEC is suspected when patients have cleft hands or feet, polydactyly, and syndactyly, abnormal development of the ectodermally derived structures, and orofacial clefting. Genitourinary (GU) anomalies have been identified in patients with EEC, yet these are often under-recognized and under-reported. The available literature on sonographic prenatal findings is sparse, especially when considering GU anomalies.

METHODS: We present the case of a male stillborn fetus, who was found antenatally to have multicystic dysplastic kidneys and anhydramnios. Following the …

A National Spinal Muscular Atrophy Registry For Real-World Evidence., Victoria L Hodgkinson, Maryam Oskoui, Joshua Lounsberry, Saïd M'Dahoma, Emily Butler, Craig Campbell, Alex Mackenzie, Hugh J Mcmillan, Louise Simard, Jiri Vajsar, Bernard Brais, Kristine M Chapman, Nicolas Chrestian, Meghan Crone, Peter Dobrowolski, Susan Dojeiji, James J Dowling, Nicolas Dupré, Angela Genge, Hernan Gonorazky, Simona Hasal, Aaron Izenberg, Wendy Johnston, Edward Leung, Hanns Lochmüller, Jean K Mah, Alier Marerro, Rami Massie, Laura Mcadam, Anna Mccormick, Michel Melanson, Michelle M Mezei, Cam-Tu E Nguyen, Colleen O'Connell, Erin K O'Ferrall, Gerald Pfeffer, Cecile Phan, Stephanie Plamondon, Chantal Poulin, Xavier Rodrigue, Kerri L Schellenberg, Kathy Selby, Jordan Sheriko, Christen Shoesmith, Garth Smith, Monique Taillon, Sean Taylor, Jodi Warman Chardon, Scott Worley, Lawrence Korngut

Paediatrics Publications

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.

METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items …

A Novel Sting1 Variant Causes A Recessive Form Of Sting-Associated Vasculopathy With Onset In Infancy (Savi)., Bin Lin, Roberta Berard, Abdulrahman Al Rasheed, Buthaina Aladba, Philip J Kranzusch, Maggie Henderlight, Alexi Grom, Dana Kahle, Sofia Torreggiani, Alexander G Aue, Jacob Mitchell, Adriana A De Jesus, Grant S Schulert, Raphaela Goldbach-Mansky

Paediatrics Publications

No abstract provided.

High Molecular Weight Adiponectin Levels Are Inversely Associated With Adiposity In Pediatric Brain Tumor Survivors., Rebecca Ronsley, Shahrad Rod Rassekh, Adam Fleming, Brianna Empringham, William Jennings, Carol Portwine, Sarah Burrow, Shayna Zelcer, Donna L Johnston, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

While children with brain tumors are surviving at record rates, survivors are at risk of cardiovascular disease and type 2 diabetes mellitus; these conditions may be driven by excess body fat. Adiponectin in an adipokine that is inversely associated with the fat mass, and has been linked to cardiometabolic risk stratification in the general population. However, adiponectin's profile and determinants in SCBT have not been established. We tested the hypothesis that high molecular weight (HMW) adiponectin levels, the more biologically active form of adiponectin, were associated with adiposity in SCBT similarly to non-cancer controls. Seventy-four SCBT (n = 32 female) …

Cardiovascular Disease Risk Assessment In Patients With Familial Mediterranean Fever Related Renal Amyloidosis., Micol Romano, David Piskin, Roberta A Berard, Bradley C Jackson, Cengizhan Acikel, Juan J Carrero, Helen J Lachmann, Mahmut I Yilmaz, Erkan Demirkaya

Paediatrics Publications

Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and …

Tam Family Receptors In Conjunction With Mapk Signalling Are Involved In Acquired Resistance To Pi3kα Inhibition In Head And Neck Squamous Cell Carcinoma., Kara M Ruicci, Jalna Meens, Paul Plantinga, William Stecho, Nicole Pinto, John Yoo, Kevin Fung, Danielle Macneil, Joe S Mymryk, John W Barrett, Christopher J Howlett, Paul C Boutros, Laurie Ailles, Anthony C Nichols

Paediatrics Publications

BACKGROUND: Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Despite pre-clinical and clinical studies, outcomes from targeting the PI3K pathway have been underwhelming and the development of drug resistance poses a significant barrier to patient treatment. In the present study, we examined mechanisms of acquired resistance to the PI3Kα inhibitor alpelisib (formerly BYL719) in HNSCC cell lines and patient-derived xenografts (PDXs).

METHODS: Five unique PDX mouse models and three HNSCC cell lines were used. All cell lines and xenografts underwent genomic characterization prior to study. Serial drug …

Developing And Implementing A Novel Mentorship Model (4+ 1) For Maternal, Newborn And Child Health In Rwanda, Anaclet Ngabonzima, Cynthia Kenyon, Celestin Hategeka, Aimee Josephine Utuza, Paulin Ruhato Banguti, Isaac Luginaah, David F Cechetto

Paediatrics Publications

BACKGROUND: There are a number of factors that may contribute to high mortality and morbidity of women and newborns in low-income countries. These include a shortage of competent health care providers (HCP) and a lack of sufficient continuous professional development (CPD) opportunities. Strengthening the skills and building the capacity of HCP involved in the provision of maternal, newborn and child health (MNCH) is essential to ensure quality care for mothers, newborns and children. To address this challenge in Rwanda, mentorship of HCPs was identified as an approach that could help build capacity, improve the provision of care and accelerate the …

A Second Cohort Of Chd3 Patients Expands The Molecular Mechanisms Known To Cause Snijders Blok-Campeau Syndrome, Theodore G Drivas, Dong Li, Divya Nair, Joseph T Alaimo, Mariëlle Alders, Janine Altmüller, Tahsin Stefan Barakat, E Martina Bebin, Nicole L Bertsch, Patrick R Blackburn, Alyssa Blesson, Arjan M Bouman, Knut Brockmann, Perrine Brunelle, Margit Burmeister, Gregory M Cooper, Jonas Denecke, Anne Dieux-Coëslier, Holly Dubbs, Alejandro Ferrer, Danna Gal, Lauren E Bartik, Lauren B Gunderson, Linda Hasadsri, Mahim Jain, Catherine Karimov, Beth Keena, Eric W Klee, Katja Kloth, Baiba Lace, Marina Macchiaiolo, Julien L Marcadier, Jeff M Milunsky, Melanie P Napier, Xilma R Ortiz-Gonzalez, Pavel N Pichurin, Jason Pinner, Zoe Powis, Chitra Prasad, Francesca Clementina Radio, Kristen J Rasmussen, Deborah L Renaud, Eric T Rush, Carol Saunders, Duygu Selcen, Ann R Seman, Deepali N Shinde, Erica D Smith, Thomas Smol, Lot Snijders Blok, Joan M Stoler, Sha Tang, Marco Tartaglia, Michelle L Thompson, Jiddeke M Van De Kamp, Jingmin Wang, Dagmar Weise, Karin Weiss, Rixa Woitschach, Bernd Wollnik, Huifang Yan, Elaine H Zackai, Giuseppe Zampino, Philippe Campeau, Elizabeth Bhoj

Paediatrics Publications

There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 (CHD3), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain. All patients were detected with unbiased molecular genetic methods. There is not a significant difference in the clinical or facial features of patients with variants in or outside this domain. These additional patients further …

Delay In Diagnosis Of Patients With Head-And-Neck Cancer In Canada: Impact Of Patient And Provider Delay., S Kassirian, A Dzioba, S Hamel, K Patel, A Sahovaler, D A Palma, N Read, V Venkatesan, A C Nichols, J Yoo, K Fung, A Mendez, S D Macneil

Paediatrics Publications

Background: Head-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting.

Methods: Patients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time …

Proceedings Of The 2019 Canadian Inflammatory Myopathy Study Symposium: Clinical Trial Readiness In Myositis., Valérie Leclair, Océane Landon-Cardinal, Rohit Aggarwal, Nick Bansback, Craig Campbell, Brian M Feldman, Martin Jarry, Suzan Mcnamara, Barbara White, Marie Hudson

Paediatrics Publications

The Canadian Inflammatory Myopathy Study (CIMS) is a multicenter prospective cohort recruiting in 8 centers across Canada. One of the aims of CIMS is to conduct and participate in clinical trials in autoimmune inflammatory myopathies (AIM). Conducting clinical trials in rare diseases such as AIM presents challenges. During this symposium, experts in the field presented different solutions to successfully conduct clinical trials in AIM, including the importance of collaboration and careful trial design, as well as training and mentoring of young investigators.

Genetic And Epigenetic Profiling Of Brca1/2 In Ovarian Tumors Reveals Additive Diagnostic Yield And Evidence Of A Genomic Brca1/2 Dna Methylation Signature, Erfan Aref-Eshghi, Jacob D. Mcgee, Victor P. Pedro, Jennifer Kerkhof, Alan Stuart, Peter J. Ainsworth, Hanxin Lin, Michael Volodarsky, Catherine Meg Mclachlin, Bekim Sadikovic

Paediatrics Publications

Poly-ADP-ribose-polymerase inhibitor (PARPi) treatment is indicated for advanced-stage ovarian tumors with BRCA1/2 deficiency. The “BRCAness” status is thought to be attributed to a tumor phenotype associated with a specific epigenomic DNA methylation profile. Here, we examined the diagnostic impact of combined BRCA1/2 sequence, copy number, and promoter DNA methylation analysis, and evaluated whether genomic DNA methylation patterns can predict the BRCAness in ovarian tumors. DNA sequencing of 172 human tissue samples of advanced-stage ovarian adenocarcinoma identified 36 samples with a clinically significant tier 1/2 sequence variants (point mutations and in/dels) and 9 samples with a CNV causing a loss of …