Publications by authors named "Moiz Bootwalla"

9 Publications

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Persistent SARS-CoV-2 infection and increasing viral variants in children and young adults with impaired humoral immunity.

medRxiv 2021 Mar 2. Epub 2021 Mar 2.

Background: There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses.

Methods: We describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape.

Findings: We found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape.

Interpretation: Our results highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered.

Funding: The work was partially funded by The Saban Research Institute at Children's Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology.
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http://dx.doi.org/10.1101/2021.02.27.21252099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941650PMC
March 2021

Early pandemic molecular diversity of SARS-CoV-2 in children.

medRxiv 2021 Feb 19. Epub 2021 Feb 19.

Background: In the US, community circulation of the SARS-CoV-2 virus likely began in February 2020 after mostly travel-related cases. Children's Hospital of Philadelphia began testing on 3/9/2020 for pediatric and adult patients, and for all admitted patients on 4/1/2020, allowing an early glimpse into the local molecular epidemiology of the virus.

Methods: We obtained 169 SARS-CoV-2 samples (83 from patients <21 years old) from March through May and produced whole genome sequences. We used genotyping tools to track variants over time and to test for possible genotype associated clinical presentations and outcomes in children.

Results: Our analysis uncovered 13 major lineages that changed in relative abundance as cases peaked in mid-April in Philadelphia. We detected at least 6 introductions of distinct viral variants into the population. As a group, children had more diverse virus genotypes than the adults tested. No strong differences in clinical variables were associated with genotypes.

Conclusions: Whole genome analysis revealed unexpected diversity, and distinct circulating viral variants within the initial peak of cases in Philadelphia. Most introductions appeared to be local from nearby states. Although limited by sample size, we found no evidence that different genotypes had different clinical impacts in children in this study.

Summary: Using sequencing and a novel technique for quantifying SARS-CoV-2 diversity, we investigated 169 SARS-CoV-2 genomes (83 <21 years old). This analysis revealed unexpected diversity especially in children. No clear differences in clinical presentation were associated with the different virus lineages.
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http://dx.doi.org/10.1101/2021.02.17.21251960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899477PMC
February 2021

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

Nat Med 2019 11 4;25(11):1680-1683. Epub 2019 Nov 4.

Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
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http://dx.doi.org/10.1038/s41591-019-0611-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898984PMC
November 2019

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants.

Cold Spring Harb Mol Case Stud 2019 04 1;5(2). Epub 2019 Apr 1.

Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.

Advancing the clinical utility of whole-exome sequencing (WES) for patients with suspected genetic disorders is largely driven by bioinformatics approaches that streamline data processing and analysis. Herein, we describe our experience with implementing a semiautomated and phenotype-driven WES diagnostic workflow, incorporating both the DRAGEN pipeline and the Exomiser variant prioritization tool, at an academic children's hospital with an ethnically diverse pediatric patient population. We achieved a 41% molecular diagnostic rate for 66 duo-, quad-, or trio-WES cases, and 28% for 40 singleton-WES cases. Preliminary results were returned to ordering physicians within 1 wk for 12 of 38 (32%) probands with positive findings, which were instrumental in guiding the appropriate clinical management for a variety of patients, especially in critical care settings. The semiautomated and streamlined WES workflow also enabled us to identify novel variants in candidate disease genes in patients with developmental delay and autism and immune disorders and cancer, including , , , , , and Together, we demonstrated the implementation of a streamlined WES workflow that was successfully applied for both clinical and research purposes.
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http://dx.doi.org/10.1101/mcs.a003756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549575PMC
April 2019

OncoKids: A Comprehensive Next-Generation Sequencing Panel for Pediatric Malignancies.

J Mol Diagn 2018 11 20;20(6):765-776. Epub 2018 Aug 20.

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California; Department of Pathology, Keck School of Medicine of USC, Los Angeles, California.

The OncoKids panel is an amplification-based next-generation sequencing assay designed to detect diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, including leukemias, sarcomas, brain tumors, and embryonal tumors. This panel uses low input amounts of DNA (20 ng) and RNA (20 ng) and is compatible with formalin-fixed, paraffin-embedded and frozen tissue, bone marrow, and peripheral blood. The DNA content of this panel covers the full coding regions of 44 cancer predisposition loci, tumor suppressor genes, and oncogenes; hotspots for mutations in 82 genes; and amplification events in 24 genes. The RNA content includes 1421 targeted gene fusions. We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies.
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http://dx.doi.org/10.1016/j.jmoldx.2018.06.009DOI Listing
November 2018

Inherited germline ATRX mutation in two brothers with ATR-X syndrome and osteosarcoma.

Am J Med Genet A 2017 May 28;173(5):1390-1395. Epub 2017 Mar 28.

Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.

We report a family in which two brothers had an undiagnosed genetic disorder comprised of dysmorphic features, microcephaly, severe intellectual disability (non-verbal), mild anemia, and cryptorchidism. Both developed osteosarcoma. Trio exome sequencing (using blood samples from the younger brother and both parents) was performed and a nonsense NM_000489.4:c.7156C>T (p.Arg2386*) mutation in the ATRX gene was identified in the proband (hemizygous) and in the mother's peripheral blood DNA (heterozygous). The mother is healthy, does not exhibit any clinical manifestations of ATR-X syndrome and there was no family history of cancer. The same hemizygous pathogenic variant was confirmed in the affected older brother's skin tissue by subsequent Sanger sequencing. Chromosomal microarray studies of both brothers' osteosarcomas revealed complex copy number alterations consistent with the clinical diagnosis of osteosarcoma. Recently, somatic mutations in the ATRX gene have been observed as recurrent alterations in both osteosarcoma and brain tumors. However, it is unclear if there is any association between osteosarcoma and germline ATRX mutations, specifically in patients with constitutional ATR-X syndrome. This is the first report of osteosarcoma diagnosed in two males with ATR-X syndrome, suggesting a potential increased risk for cancer in patients with this disorder.
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http://dx.doi.org/10.1002/ajmg.a.38184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521841PMC
May 2017

Generation and characterization of tamoxifen-inducible Pax9-CreER knock-in mice using CrispR/Cas9.

Genesis 2016 09 26;54(9):490-6. Epub 2016 Jul 26.

Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, 90033, USA.

Pax9 encodes a paired-box homeodomain (Pax) transcription factor and is critical for the development of multiple organs. Using CrispR/Cas9-mediated homologous directed repair (HDR), we generated a new Pax9-CreER knock-in mouse line in which the CreER(T2) fusion protein is produced after synthesis of endogenous Pax9 protein. We found that tdTomato reporter expression in Pax9-CreER;tdTomato reporter mice is detectable in a similar pattern to the endogenous Pax9 expression, faithfully recapitulating the Pax9 expression domains throughout the embryo and in the adult mouse. At early embryonic stages, the tdTomato reporter is expressed first in the pharyngeal pouch region and later in the craniofacial mesenchyme, somites, limbs, and lingual papillae in the adult tongue. These results demonstrate that this new Pax9-CreER knock-in mouse line can be used for lineage tracing and genetic targeting of Pax9-expressing cells and their progeny in a temporally and spatially controlled manner during development and organogenesis.
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http://dx.doi.org/10.1002/dvg.22956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021577PMC
September 2016

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

Authors:
W Marston Linehan Paul T Spellman Christopher J Ricketts Chad J Creighton Suzanne S Fei Caleb Davis David A Wheeler Bradley A Murray Laura Schmidt Cathy D Vocke Myron Peto Abu Amar M Al Mamun Eve Shinbrot Anurag Sethi Samira Brooks W Kimryn Rathmell Angela N Brooks Katherine A Hoadley A Gordon Robertson Denise Brooks Reanne Bowlby Sara Sadeghi Hui Shen Daniel J Weisenberger Moiz Bootwalla Stephen B Baylin Peter W Laird Andrew D Cherniack Gordon Saksena Scott Haake Jun Li Han Liang Yiling Lu Gordon B Mills Rehan Akbani Mark D M Leiserson Benjamin J Raphael Pavana Anur Donald Bottaro Laurence Albiges Nandita Barnabas Toni K Choueiri Bogdan Czerniak Andrew K Godwin A Ari Hakimi Thai H Ho James Hsieh Michael Ittmann William Y Kim Bhavani Krishnan Maria J Merino Kenna R Mills Shaw Victor E Reuter Ed Reznik Carl S Shelley Brian Shuch Sabina Signoretti Ramaprasad Srinivasan Pheroze Tamboli George Thomas Satish Tickoo Kenneth Burnett Daniel Crain Johanna Gardner Kevin Lau David Mallery Scott Morris Joseph D Paulauskis Robert J Penny Candace Shelton W Troy Shelton Mark Sherman Eric Thompson Peggy Yena Melissa T Avedon Jay Bowen Julie M Gastier-Foster Mark Gerken Kristen M Leraas Tara M Lichtenberg Nilsa C Ramirez Tracie Santos Lisa Wise Erik Zmuda John A Demchok Ina Felau Carolyn M Hutter Margi Sheth Heidi J Sofia Roy Tarnuzzer Zhining Wang Liming Yang Jean C Zenklusen Jiashan Zhang Brenda Ayala Julien Baboud Sudha Chudamani Jia Liu Laxmi Lolla Rashi Naresh Todd Pihl Qiang Sun Yunhu Wan Ye Wu Adrian Ally Miruna Balasundaram Saianand Balu Rameen Beroukhim Tom Bodenheimer Christian Buhay Yaron S N Butterfield Rebecca Carlsen Scott L Carter Hsu Chao Eric Chuah Amanda Clarke Kyle R Covington Mahmoud Dahdouli Ninad Dewal Noreen Dhalla Harsha V Doddapaneni Jennifer A Drummond Stacey B Gabriel Richard A Gibbs Ranabir Guin Walker Hale Alicia Hawes D Neil Hayes Robert A Holt Alan P Hoyle Stuart R Jefferys Steven J M Jones Corbin D Jones Divya Kalra Christie Kovar Lora Lewis Jie Li Yussanne Ma Marco A Marra Michael Mayo Shaowu Meng Matthew Meyerson Piotr A Mieczkowski Richard A Moore Donna Morton Lisle E Mose Andrew J Mungall Donna Muzny Joel S Parker Charles M Perou Jeffrey Roach Jacqueline E Schein Steven E Schumacher Yan Shi Janae V Simons Payal Sipahimalani Tara Skelly Matthew G Soloway Carrie Sougnez Angela Tam Donghui Tan Nina Thiessen Umadevi Veluvolu Min Wang Matthew D Wilkerson Tina Wong Junyuan Wu Liu Xi Jane Zhou Jason Bedford Fengju Chen Yao Fu Mark Gerstein David Haussler Katayoon Kasaian Phillip Lai Shiyun Ling Amie Radenbaugh David Van Den Berg John N Weinstein Jingchun Zhu Monique Albert Iakovina Alexopoulou Jeremiah J Andersen J Todd Auman John Bartlett Sheldon Bastacky Julie Bergsten Michael L Blute Lori Boice Roni J Bollag Jeff Boyd Erik Castle Ying-Bei Chen John C Cheville Erin Curley Benjamin Davies April DeVolk Rajiv Dhir Laura Dike John Eckman Jay Engel Jodi Harr Ronald Hrebinko Mei Huang Lori Huelsenbeck-Dill Mary Iacocca Bruce Jacobs Michael Lobis Jodi K Maranchie Scott McMeekin Jerome Myers Joel Nelson Jeremy Parfitt Anil Parwani Nicholas Petrelli Brenda Rabeno Somak Roy Andrew L Salner Joel Slaton Melissa Stanton R Houston Thompson Leigh Thorne Kelinda Tucker Paul M Weinberger Cynthia Winemiller Leigh Anne Zach Rosemary Zuna

N Engl J Med 2016 Jan 4;374(2):135-45. Epub 2015 Nov 4.

Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist.

Methods: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.

Results: Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH).

Conclusions: Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
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http://dx.doi.org/10.1056/NEJMoa1505917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775252PMC
January 2016

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

Authors:
Daniel J Brat Roel G W Verhaak Kenneth D Aldape W K Alfred Yung Sofie R Salama Lee A D Cooper Esther Rheinbay C Ryan Miller Mark Vitucci Olena Morozova A Gordon Robertson Houtan Noushmehr Peter W Laird Andrew D Cherniack Rehan Akbani Jason T Huse Giovanni Ciriello Laila M Poisson Jill S Barnholtz-Sloan Mitchel S Berger Cameron Brennan Rivka R Colen Howard Colman Adam E Flanders Caterina Giannini Mia Grifford Antonio Iavarone Rajan Jain Isaac Joseph Jaegil Kim Katayoon Kasaian Tom Mikkelsen Bradley A Murray Brian Patrick O'Neill Lior Pachter Donald W Parsons Carrie Sougnez Erik P Sulman Scott R Vandenberg Erwin G Van Meir Andreas von Deimling Hailei Zhang Daniel Crain Kevin Lau David Mallery Scott Morris Joseph Paulauskis Robert Penny Troy Shelton Mark Sherman Peggy Yena Aaron Black Jay Bowen Katie Dicostanzo Julie Gastier-Foster Kristen M Leraas Tara M Lichtenberg Christopher R Pierson Nilsa C Ramirez Cynthia Taylor Stephanie Weaver Lisa Wise Erik Zmuda Tanja Davidsen John A Demchok Greg Eley Martin L Ferguson Carolyn M Hutter Kenna R Mills Shaw Bradley A Ozenberger Margi Sheth Heidi J Sofia Roy Tarnuzzer Zhining Wang Liming Yang Jean Claude Zenklusen Brenda Ayala Julien Baboud Sudha Chudamani Mark A Jensen Jia Liu Todd Pihl Rohini Raman Yunhu Wan Ye Wu Adrian Ally J Todd Auman Miruna Balasundaram Saianand Balu Stephen B Baylin Rameen Beroukhim Moiz S Bootwalla Reanne Bowlby Christopher A Bristow Denise Brooks Yaron Butterfield Rebecca Carlsen Scott Carter Lynda Chin Andy Chu Eric Chuah Kristian Cibulskis Amanda Clarke Simon G Coetzee Noreen Dhalla Tim Fennell Sheila Fisher Stacey Gabriel Gad Getz Richard Gibbs Ranabir Guin Angela Hadjipanayis D Neil Hayes Toshinori Hinoue Katherine Hoadley Robert A Holt Alan P Hoyle Stuart R Jefferys Steven Jones Corbin D Jones Raju Kucherlapati Phillip H Lai Eric Lander Semin Lee Lee Lichtenstein Yussanne Ma Dennis T Maglinte Harshad S Mahadeshwar Marco A Marra Michael Mayo Shaowu Meng Matthew L Meyerson Piotr A Mieczkowski Richard A Moore Lisle E Mose Andrew J Mungall Angeliki Pantazi Michael Parfenov Peter J Park Joel S Parker Charles M Perou Alexei Protopopov Xiaojia Ren Jeffrey Roach Thaís S Sabedot Jacqueline Schein Steven E Schumacher Jonathan G Seidman Sahil Seth Hui Shen Janae V Simons Payal Sipahimalani Matthew G Soloway Xingzhi Song Huandong Sun Barbara Tabak Angela Tam Donghui Tan Jiabin Tang Nina Thiessen Timothy Triche David J Van Den Berg Umadevi Veluvolu Scot Waring Daniel J Weisenberger Matthew D Wilkerson Tina Wong Junyuan Wu Liu Xi Andrew W Xu Lixing Yang Travis I Zack Jianhua Zhang B Arman Aksoy Harindra Arachchi Chris Benz Brady Bernard Daniel Carlin Juok Cho Daniel DiCara Scott Frazer Gregory N Fuller JianJiong Gao Nils Gehlenborg David Haussler David I Heiman Lisa Iype Anders Jacobsen Zhenlin Ju Sol Katzman Hoon Kim Theo Knijnenburg Richard Bailey Kreisberg Michael S Lawrence William Lee Kalle Leinonen Pei Lin Shiyun Ling Wenbin Liu Yingchun Liu Yuexin Liu Yiling Lu Gordon Mills Sam Ng Michael S Noble Evan Paull Arvind Rao Sheila Reynolds Gordon Saksena Zack Sanborn Chris Sander Nikolaus Schultz Yasin Senbabaoglu Ronglai Shen Ilya Shmulevich Rileen Sinha Josh Stuart S Onur Sumer Yichao Sun Natalie Tasman Barry S Taylor Doug Voet Nils Weinhold John N Weinstein Da Yang Kosuke Yoshihara Siyuan Zheng Wei Zhang Lihua Zou Ty Abel Sara Sadeghi Mark L Cohen Jenny Eschbacher Eyas M Hattab Aditya Raghunathan Matthew J Schniederjan Dina Aziz Gene Barnett Wendi Barrett Darell D Bigner Lori Boice Cathy Brewer Chiara Calatozzolo Benito Campos Carlos Gilberto Carlotti Timothy A Chan Lucia Cuppini Erin Curley Stefania Cuzzubbo Karen Devine Francesco DiMeco Rebecca Duell J Bradley Elder Ashley Fehrenbach Gaetano Finocchiaro William Friedman Jordonna Fulop Johanna Gardner Beth Hermes Christel Herold-Mende Christine Jungk Ady Kendler Norman L Lehman Eric Lipp Ouida Liu Randy Mandt Mary McGraw Roger Mclendon Christopher McPherson Luciano Neder Phuong Nguyen Ardene Noss Raffaele Nunziata Quinn T Ostrom Cheryl Palmer Alessandro Perin Bianca Pollo Alexander Potapov Olga Potapova W Kimryn Rathmell Daniil Rotin Lisa Scarpace Cathy Schilero Kelly Senecal Kristen Shimmel Vsevolod Shurkhay Suzanne Sifri Rosy Singh Andrew E Sloan Kathy Smolenski Susan M Staugaitis Ruth Steele Leigh Thorne Daniela P C Tirapelli Andreas Unterberg Mahitha Vallurupalli Yun Wang Ronald Warnick Felicia Williams Yingli Wolinsky Sue Bell Mara Rosenberg Chip Stewart Franklin Huang Jonna L Grimsby Amie J Radenbaugh Jianan Zhang

N Engl J Med 2015 Jun 10;372(26):2481-98. Epub 2015 Jun 10.

Background: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas.

Methods: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes.

Results: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma.

Conclusions: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).
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http://dx.doi.org/10.1056/NEJMoa1402121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530011PMC
June 2015