Medical Specialties Commons^™

Differential Phenotypes Of Memory Cd4 And Cd8 T Cells In The Spleen And Peripheral Tissues Following Immunostimulatory Therapy., Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka R Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy

Articles, Abstracts, and Reports

BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative …

Persuasive Interventions For Controversial Cancer Screening Recommendations: Testing A Novel Approach To Help Patients Make Evidence-Based Decisions., Barry Saver, Kathleen M Mazor, Roger Luckmann, Sarah L Cutrona, Marcela Hayes, Tatyana Gorodetsky, Nancy Esparza, Gonzalo Bacigalupe

Articles, Abstracts, and Reports

PURPOSE: We wanted to evaluate novel decision aids designed to help patients trust and accept the controversial, evidence-based, US Preventive Services Task Force recommendations about prostate cancer screening (from 2012) and mammography screening for women aged 40 to 49 years (from 2009).

METHODS: We created recorded vignettes of physician-patient discussions about prostate cancer screening and mammography, accompanied by illustrative slides, based on principles derived from preceding qualitative work and behavioral science literature. We conducted a randomized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years. All participants saw …

Astrocytes Promote Progression Of Breast Cancer Metastases To The Brain Via A Kiss1-Mediated Autophagy., Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov

Articles, Abstracts, and Reports

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level …

Persistence Of Low Disease Activity After Tumour Necrosis Factor Inhibitor (Tnfi) Discontinuation In Patients With Psoriatic Arthritis., D H Huynh, T A Boyd, C J Etzel, V Cox, J Kremer, P Mease, A Kavanaugh

Articles, Abstracts, and Reports

OBJECTIVE: To determine the duration of clinical benefit among patients with psoriatic arthritis (PsA) discontinuing tumour necrosis factor inhibitor (TNFi) therapy while in low disease activity (LDA), and to identify patient characteristics associated with prolonged clinical benefit.

METHODS: We performed an observational cohort study assessing patients with PsA from the Consortium of Rheumatology Researchers of North America (CORRONA) registry who had discontinued TNFi after achieving LDA, defined as clinical disease activity index (CDAI) score ≤10 and physician's global assessment (PGA) of skin psoriasis ≤20/100. Kaplan-Meier method was used to estimate the duration of clinical benefit.

RESULTS: Of the 5945 patients …

A Journey Of Educational Transformation And Organizational Improvement Through Development Of An Institutional Patient Blood Management Program, Robert Raggi, Karen Klein, Marci Swearingen, Mark Domantay

Articles, Abstracts, and Reports

Providence Holy Cross Medical Center (PHCMC) has embarked on this journey to improve outcomes by reducing the number of unnecessary transfusions through the development of a PBM program. Transfusion-related health risks and increasing economic pressures have driven hospitals to recognize development of blood management programs as an important strategy to improve patient outcomes and reduce costs.

Interpretation Of Positive Troponin Results Among Patients With And Without Myocardial Infarction., Kristen M Tecson, William Arnold, Tyler Barrett, Robert Birkhahn, Lori B Daniels, Christopher Defilippi, Gary Headden, W Frank Peacock, Michael Reed, Adam J Singer, Jeffrey M Schussler, Stephen Smith, Martin P Than, Peter A Mccullough

Articles, Abstracts, and Reports

Measuring cardiac troponins is integral to diagnosing acute myocardial infarction (AMI); however, troponins may be elevated without AMI, and the use of multiple different assays confounds comparisons. We considered characteristics and serial troponin values in emergency department chest pain patients with and without AMI to interpret troponin excursions. We compared serial troponin in 124 AMI and non-AMI patients from the observational Performance of Triage Cardiac Markers in the Clinical Setting (PEARL) study who presented with chest pain and had at least one troponin value exceeding the 99th percentile of normal. Because 8 assays were used during data collection, we employed …

Mutational Landscapes Of Smoking-Related Cancers In Caucasians And African Americans: Precision Oncology Perspectives At Wake Forest Baptist Comprehensive Cancer Center., Ville Kytola, Umit Topaloglu, Lance D Miller, Rhonda L Bitting, Michael M Goodman, Ralph B D Agostino, Rodwige J Desnoyers, Carol Albright, George Yacoub, Shadi A Qasem, Barry Deyoung, Vesteinn Thorsson, Ilya Shmulevich, Meng Yang, Anastasia Shcherban, Matthew Pagni, Liang Liu, Matti Nykter, Kexin Chen, Gregory A Hawkins, Stefan C Grant, W Jeffrey Petty, Angela Tatiana Alistar, Edward A Levine, Edgar D Staren, Carl D Langefeld, Vincent Miller, Gaurav Singal, Robin M Petro, Mac Robinson, William Blackstock, Bayard L Powell, Lynne I Wagner, Kristie L Foley, Edward Abraham, Boris Pasche, Wei Zhang

Articles, Abstracts, and Reports

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high …

Peripheral Huntingtin Silencing Does Not Ameliorate Central Signs Of Disease In The B6.Httq111/+ Mouse Model Of Huntington's Disease., Sydney R Coffey, Robert M Bragg, Shawn Minnig, Seth A Ament, Jeffrey P Cantle, Anne Glickenhaus, Daniel Shelnut, José M Carrillo, Dominic D Shuttleworth, Julie-Anne Rodier, Kimihiro Noguchi, C Frank Bennett, Nathan D Price, Holly B Kordasiewicz, Jeffrey B Carroll

Articles, Abstracts, and Reports

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease whose predominant neuropathological signature is the selective loss of medium spiny neurons in the striatum. Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. We, and others, have suggested that peripheral dysfunction could contribute to the rate of progression of striatal phenotypes of HD. To test this hypothesis, we lowered levels of huntingtin by treating mice with antisense oligonucleotides (ASOs) targeting the murine …

A Randomized Study Comparing Digital Imaging To Traditional Glass Slide Microscopy For Breast Biopsy And Cancer Diagnosis., Joann G Elmore, Gary M Longton, Margaret S Pepe, Patricia A Carney, Heidi D Nelson, Kimberly H Allison, Berta M Geller, Tracy Onega, Anna N A Tosteson, Ezgi Mercan, Linda G Shapiro, Tad T Brunyé, Thomas R Morgan, Donald L Weaver

Articles, Abstracts, and Reports

BACKGROUND: Digital whole slide imaging may be useful for obtaining second opinions and is used in many countries. However, the U.S. Food and Drug Administration requires verification studies.

METHODS: Pathologists were randomized to interpret one of four sets of breast biopsy cases during two phases, separated by ≥9 months, using glass slides or digital format (sixty cases per set, one slide per case,

RESULTS: Sixty-five percent of responding pathologists were eligible, and 252 consented to randomization; 208 completed Phase I (115 glass, 93 digital); and 172 completed Phase II (86 glass, 86 digital). Accuracy was slightly higher using glass compared …

Does Gated Beam Delivery Impact Delivery Accuracy On An Elekta Linac?, Mohammed Jermoumi, Roger Xie, Daliang Cao, David J Housley, David M Shepard

Articles, Abstracts, and Reports

In this study, we evaluated the performance of an Elekta linac in the delivery of gated radiotherapy. Delivery accuracy was examined with an emphasis on the impact of using short gating windows (low monitor unit beam-on segments) or long beam hold times. The performance was assessed using a 20cm by 20cm open field with the radiation delivered using a range of beam-on and beam-off time periods. Gated delivery measurements were also performed for two SBRT plans delivered using volumetric modulated arc therapy (VMAT). Tests included both free-breathing based gating (covering a variety of gating windows) and simulated breath-hold based gating. …

A Previously Unreported Arterial Variant Of The Suboccipital Region Based On Cadaveric Dissection., Christian Fisahn, Brittni Burgess, Joe Iwanaga, Fernando Alonso, Jens R Chapman, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

No abstract provided.

New Cancer Immunotherapy Agents In Development: A Report From An Associated Program Of The 31, Prasad S Adusumilli, Edward Cha, Mark Cornfeld, Thomas Davis, Adi Diab, Thomas W Dubensky, Elizabeth Evans, Jane L Grogan, Bryan A Irving, Rom Leidner, Shane A Olwill, Patrick Soon-Shiong, Frederic Triebel, David Tuck, Adrian Bot, Roger D Dansey, Charles G Drake, Gordon J Freeman, Ramy Ibrahim, Salil Patel, Daniel S Chen

Articles, Abstracts, and Reports

This report is a summary of 'New Cancer Immunotherapy Agents in Development' program, which took place in association with the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), on November 9, 2016 in National Harbor, Maryland. Presenters gave brief overviews of emerging clinical and pre-clinical immune-based agents and combinations, before participating in an extended panel discussion with multidisciplinary leaders, including members of the FDA, leading academic institutions and industrial drug developers, to consider topics relevant to the future of cancer immunotherapy.

The Promise Of Systems Biology Approaches For Revealing Host Pathogen Interactions In Malaria., Meghan Zuck, Laura S Austin, Samuel A Danziger, John D Aitchison, Alexis Kaushansky

Articles, Abstracts, and Reports

Despite global eradication efforts over the past century, malaria remains a devastating public health burden, causing almost half a million deaths annually (WHO, 2016). A detailed understanding of the mechanisms that control malaria infection has been hindered by technical challenges of studying a complex parasite life cycle in multiple hosts. While many interventions targeting the parasite have been implemented, the complex biology of

Safety And Feasibility Of Minimally Invasive Inguinal Lymph Node Dissection In Patients With Melanoma (Safe-Milnd): Report Of A Prospective Multi-Institutional Trial., James W Jakub, Alicia M Terando, Amod Sarnaik, Charlotte E Ariyan, Mark Faries, Sabino Zani, Heather B Neuman, Nabil Wasif, Jeffrey M Farma, Bruce J Averbook, Karl Y Bilimoria, Travis E Grotz, Jacob B Jake Allred, Vera J Suman, Mary Sue Brady, Douglas Tyler, Jeffrey D Wayne, Heidi Nelson

Articles, Abstracts, and Reports

BACKGROUND: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure.

METHODS: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria …

Prediction And Benefits Of Minimal Disease Activity In Patients With Psoriatic Arthritis And Active Skin Disease In The Adept Trial., Philip Mease, Arthur Kavanaugh, Laura C Coates, Iain B Mcinnes, Maja Hojnik, Ying Zhang, Jaclyn K Anderson, Alexander P Dorr, Dafna D Gladman

Articles, Abstracts, and Reports

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs).

Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent …

Cigarette Smoking And Cardio-Renal Events In Patients With Atherosclerotic Renal Artery Stenosis., Christopher A Drummond, Pamela S Brewster, Wencan He, Kaili Ren, Yanmei Xie, Katherine Tuttle, Steven T Haller, Kenneth Jamerson, Lance D Dworkin, Donald E Cutlip, Timothy P Murphy, Ralph B D'Agostino, William L Henrich, Jiang Tian, Joseph I Shapiro, Christopher J Cooper

Articles, Abstracts, and Reports

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p

Community Collaboration To Decrease Atypical Emergency Department Utilization, Becky Wilkinson

Articles, Abstracts, and Reports

No abstract provided.

Insights Into Local Tumor Microenvironment Immune Factors Associated With Regression Of Cutaneous Melanoma Metastases By, Junbao Yang, Maris S Jones, Romela Irene Ramos, Alfred A Chan, Agnes F Lee, Leland J Foshag, Peter A Sieling, Mark Faries, Delphine J Lee

Articles, Abstracts, and Reports

No abstract provided.

Prognostic Value Of Multiple Draining Lymph Node Basins In Melanoma: A Matched-Pair Analysis Based On The John Wayne Cancer Institute Experience., J Harrison Howard, Junko J Ozao-Choy, Jason M Hiles, Myung-Shin Sim, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND: The prognostic significance of multiple draining basins is controversial in melanoma because analyses have not adequately controlled for standard prognostic variables. We hypothesized that an analysis based on prognostically matched pairs of patients with multiple versus single drainage basins would clarify any independent role of basin number.

STUDY DESIGN: We identified patients in our 40-year prospective database, who underwent preoperative lymphoscintigraphy, intraoperative sentinel node biopsy and wide local excision for cutaneous melanoma. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared in patients with multiple versus single drainage basins after matching by age, sex, Breslow depth, …

Prevalence And Correlates Of Cannabis Use In Outpatients With Serious Mental Illness Receiving Treatment For Alcohol Use Disorders., Jordan Skalisky, Emily Leickly, Oladunni Oluwoye, Sterling M Mcpherson, Debra Srebnik, John M Roll, Richard K Ries, Michael G Mcdonell

Articles, Abstracts, and Reports

Introduction: People with serious mental illness (SMI) use cannabis more than any other illicit drug. Cannabis use is associated with increased psychotic symptoms and is highly comorbid with alcohol use disorders (AUDs). Despite the national trend toward decriminalization, little is known about the prevalence, correlates, and impact of cannabis use on those with SMI receiving treatment for substance use disorders, a group at high risk for the negative effects of cannabis use. Methods: In this secondary data analysis, cannabis use prevalence, correlates, and impact on treatment outcomes were examined in 121 adults with cooccurring SMI and AUDs receiving outpatient addiction …

Unresectable Hepatoblastoma: Current Perspectives., Angela D Trobaugh-Lotrario, Rebecka L Meyers, Allison F O'Neill, James H Feusner

Articles, Abstracts, and Reports

Although rare, hepatoblastoma is the most common pediatric liver tumor. Complete resection is a critical component for cure; however, most patients will have tumors that are not resected at diagnosis. For these patients, administration of neoadjuvant chemotherapy renders tumors resectable in most patients. For patients whose tumors remain unresectable after chemotherapy, liver transplantation is indicated (in the absence of active unresectable metastatic disease). In patients whose tumors remain unresectable after conventional chemotherapy, interventional techniques may serve as a promising option to reduce tumor size, decrease systemic toxicity, decrease need for liver transplantation, and increase feasibility of tumor resection.

Ion Channel Expression Patterns In Glioblastoma Stem Cells With Functional And Therapeutic Implications For Malignancy., Julia Pollak, Karan G Rai, Cory C Funk, Sonali Arora, Eunjee Lee, Jun Zhu, Nathan D Price, Patrick J Paddison, Jan-Marino Ramirez, Robert C Rostomily

Articles, Abstracts, and Reports

Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression …

Preoperative Immunonutrition And Elective Colorectal Resection Outcomes., Lucas W Thornblade, Thomas K Varghese, Xu Shi, Eric K Johnson, Amir Bastawrous, Richard P Billingham, Richard Thirlby, Alessandro Fichera, David R Flum

Articles, Abstracts, and Reports

BACKGROUND: Randomized controlled trials demonstrate the efficacy of arginine-enriched nutritional supplements (immunonutrition) in reducing complications after surgery. The effectiveness of preoperative immunonutrition has not been evaluated in a community setting.

OBJECTIVE: This study aims to determine whether immunonutrition before elective colorectal surgery improves outcomes in the community at large.

DESIGN: This is a prospective cohort study with a propensity score-matched comparative effectiveness evaluation.

SETTINGS: This study was conducted in Washington State hospitals in the Surgical Care Outcomes Assessment Program from 2012 to 2015.

PATIENTS: Adults undergoing elective colorectal surgery were selected.

INTERVENTIONS: Surgeons used a preoperative checklist that recommended that …

Risk Of Glucose Intolerance And Gestational Diabetes Mellitus In Relation To Maternal Habitual Snoring During Early Pregnancy., Chunfang Qiu, Wayne Lawrence, Bizu Gelaye, Lee Stoner, Ihunnaya O Frederick, Daniel A Enquobahrie, Tanya K Sorensen, Michelle A Williams

Articles, Abstracts, and Reports

BACKGROUND: Obstructive sleep apnea (OSA) or habitual snoring is known to be associated with impaired glucose tolerance and type 2 diabetes among both men and non-pregnant women. We examined the association of habitual snoring during early pregnancy with risk of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM).

METHODS: A cohort of 1,579 women was interviewed during early pregnancy. We collected information about snoring frequency during early pregnancy. Results from screening and diagnostic tests for IGT and GDM were abstracted from medical records. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% …

Assessing Survival And Grading The Severity Of Complications In Octogenarians Undergoing Pulmonary Lobectomy., Andrew Feczko, Elizabeth Mckeown, Jennifer L Wilson, Brian E Louie, Ralph W Aye, Jed A Gorden, Eric Vallières, Alexander S Farivar

Articles, Abstracts, and Reports

No abstract provided.

Histopathology And Enhanced Detection Of Tumor Invasion Of Peritoneal Membranes., Jey-Hsin Chen, Melissa Borges

Articles, Abstracts, and Reports

Tumor invasion of the peritoneal membrane may have an adverse prognostic significance, but its histopathologic features can be diagnostically difficult to recognize. We observed that local peritoneal injury associated with tumor invasion is characterized by activation and proliferation of serosal stromal cells that express cytokeratin, a characteristic property of injured serosal membranes that may have diagnostic utility. To explore this, we examined 120 primary tumors of the gastrointestinal tract and pancreaticobiliary system using cytokeratin and elastic stains to assess for tumor invasion of peritoneal membranes. Peritoneal invasion by tumor was associated with retraction, splaying, and destruction of the elastic lamina …

Logic Models To Predict Continuous Outputs Based On Binary Inputs With An Application To Personalized Cancer Therapy., Theo A Knijnenburg, Gunnar W Klau, Francesco Iorio, Mathew J Garnett, Ultan Mcdermott, Ilya Shmulevich, Lodewyk F A Wessels

Articles, Abstracts, and Reports

Mining large datasets using machine learning approaches often leads to models that are hard to interpret and not amenable to the generation of hypotheses that can be experimentally tested. We present 'Logic Optimization for Binary Input to Continuous Output' (LOBICO), a computational approach that infers small and easily interpretable logic models of binary input features that explain a continuous output variable. Applying LOBICO to a large cancer cell line panel, we find that logic combinations of multiple mutations are more predictive of drug response than single gene predictors. Importantly, we show that the use of the continuous information leads to …

Quantitative Proteomic Analysis Of Stratum Corneum Dysfunction In Adult Chronic Atopic Dermatitis., Jason M Winget, Deborah Finlay, Kevin J Mills, Tom Huggins, Charles Bascom, Robert J Isfort, Robert L Moritz

Articles, Abstracts, and Reports

No abstract provided.

Characterization Of The Microbiome Of Nipple Aspirate Fluid Of Breast Cancer Survivors., Alfred A Chan, Mina Bashir, Magali N Rivas, Karen Duvall, Peter A Sieling, Thomas R Pieber, Parag A Vaishampayan, Susan M Love, Delphine J Lee

Articles, Abstracts, and Reports

The microbiome impacts human health and disease. Until recently, human breast tissue and milk were presumed to be sterile. Here, we investigated the presence of microbes in the nipple aspirate fluid (NAF) and their potential association with breast cancer. We compared the NAF microbiome between women with a history of breast cancer (BC) and healthy control women (HC) using 16S rRNA gene amplicon sequencing. The NAF microbiome from BC and HC showed significant differences in community composition. Two Operational Taxonomic Units (OTUs) showed differences in relative abundances between NAF collected from BC and HC. In NAF collected from BC, there …

Pik3ca-Associated Developmental Disorders Exhibit Distinct Classes Of Mutations With Variable Expression And Tissue Distribution, Ghayda Mirzaa, Andrew E Timms, Valerio Conti, Evan August Boyle, Katta M Girisha, Beth Martin, Martin Kircher, Carissa Olds, Jane Juusola, Sarah Collins, Kaylee Park, Melissa Carter, Ian Glass, Inge Krägeloh-Mann, David Chitayat, Aditi Shah Parikh, Rachael Bradshaw, Erin Torti, Stephen Braddock, Leah Burke, Sondhya Ghedia, Mark Stephan, Fiona Stewart, Chitra Prasad, Melanie Napier, Sulagna Saitta, Rachel Straussberg, Michael Gabbett, Bridget C O'Connor, Catherine E Keegan, Lim Jiin Yin, Angeline Hwei Meeng Lai, Nicole Martin, Margaret Mckinnon, Marie-Claude Addor, Luigi Boccuto, Charles E Schwartz, Agustina Lanoel, Robert L Conway, Koenraad Devriendt, Katrina Tatton-Brown, Mary Ella Pierpont, Michael Painter, Lisa Worgan, James Reggin, Raoul Hennekam, Karen Tsuchiya, Colin C Pritchard, Mariana Aracena, Karen W Gripp, Maria Cordisco, Hilde Van Esch, Livia Garavelli, Cynthia Curry, Anne Goriely, Hulya Kayserilli, Jay Shendure, John Graham, Renzo Guerrini, William B Dobyns

Articles, Abstracts, and Reports

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing ( …