Genomic analysis of childhood High grade glial (HGG) brain tumors
|
|
- Dana Caldwell
- 6 years ago
- Views:
Transcription
1 Genomic analysis of childhood High grade glial (HGG) brain tumors Linda D Cooley Children s Mercy, Kansas City The Children s Mercy Hospital, 2017
2 Genomic analysis of childhood High grade glial (HGG) brain tumors IRB approved retrospective study Funded by a Children s Mercy Cancer Center grant October 2016-September 2018 Authors declare no conflicts
3 Pediatric High Grade Glial Tumors High grade gliomas (HGG) comprise ~8 12% of primary pediatric CNS tumors. HGG are aggressive tumors classified by the World Health Organization (WHO) as grade III or IV. Tumor histology - spectrum - with hypercellularity, nuclear atypia, high mitotic activity, plus/minus microvascular proliferation and necrosis. Outcomes remain dismal - 5-year survival ranges from 15 to 35%. Key to improving survival - better understanding of tumor biology. Genetic data show pediatric HGG are distinct from adult HGG.
4 Specific aims of study 1. Interrogate archival HGG brain tumors for copy number aberrations, loss of heterozygosity, and select somatic mutations using the Affymetrix Oncoscan microarray. 2. Review data from previous clinical Pathology, Cytogenetic, and Molecular reports and review patient Medical Records for clinical characteristics. 3. Correlate genetic alterations with histopathological findings and clinical characteristics.
5 Archival HGG brain tumors Tumor samples - selected & reviewed by Neuropathologist 42 FFPE samples from CMH archives ( ) 33 unique patients; 4 patients had recurrent tumor resections 2 autopsy and 31 surgical samples
6 Pathology Pathology 16 supratentorial, 4 infratentorial (cerebellum), 13 midline (brainstem, thalamus, basal ganglia) WHO tumor grade: Grade III (AA) -15 Grade IV (GBM) 18 Gender 15 male : 18 female patients Patient age range 5 months - 17 years Average age 9.7 yrs; median age 10 yr
7 Methods Affymetrix Oncoscan Molecular Inversion Probe technology DNA isolated using Promega Maxwell RSC FFPE kit Sanger sequencing Microarray analyzed using Affymetrix ChAS software and Biodiscovery Nexus Express software Review previous clinical chromosome, FISH, molecular results Medical records review & data collection by data manager Limited statistical analysis
8 Chromosomes and microarray 25/33 (76%) tumors had chromosome analysis 7 had no chromosomes ordered, 1 failure 20/25 (80%) had abnormal karyotype 5 normal karyotype 1 had BRAF-KIAA1549 duplication only 33/33 (100%) tumors had abnormal microarray
9 Number of cases Oncoscan whole chromosome / chromosome arm Copy Number aberrations / LOH q 2 5p 5q 6p 6q 7 9p 10p 10q 12 13q 17p 18 Gain Loss LOH
10 Copy Number Aberrations (Percent) Adult Pediatric TCGA/WHO Current Bax 2010 Paugh q gain 9 48 (33) 19 (63) 29 (68) chr 7 gain p LOH/loss ~30 mut q loss q loss q loss 8-12 mut CDKN2A del up to PDGFRA amp EGFR amp
11 Genomic profiles (as define by Bax, etal. Clin Cancer Res 2010) 3 (9%) Stable genome few (<3), low level, focal changes 7 (21%) Amplifier amplification 8 (24%) Aneuploid large, single copy alterations of whole chromosomes or chromosome arms 15 (46%) Rearranged numerous, low-level, intrachromosomal breaks resulting in multiple gains & losses and a highly rearranged genome
12 Genomic subtypes of pediatric high-grade glioma have prognostic relevance (Bax). Dorine A. Bax et al. Clin Cancer Res 2010;16:
13 Genome classification vs age, location, grade Stable younger, supratentorial, grade III Aneuploid older, supratentorial, grade III Rearranged older, supratentorial, grade IV Amplifier older, midline, grade IV
14 Stable genome 3/33 (9%) Stable genome 1 with BRAF-KIAA1549 duplication fusion 1 with htz 9p loss & hmz CDKN2A/B loss 1 with ROS1-GOPC deletion fusion - activation of RTK ROS1 Younger age (5, 6, 15 mo), 2 of 3 supratentorial, 2 of 3 WHO grade III Survival 0, 4, 5 mo Death average survival 3 months
15 Aneuploid genome favorable 8/33 (24%) Aneuploid LOH/loss 1p Gain 1q, 5p, 7, 12, 19p, 20 1 with ROS1-GOPC deletion fusion Older age, supratentorial location, WHO grade III Death of two pts at 4 mo & 39 mo Survival 6 patients 13, 9, 6 years, 21, 17, & 7 months average survival 4.7 years
16 Rearranged genome unfavorable 15/33 (46%) Rearranged LOH 17p Loss 17p,13q, 5q, 9p, 22q, 6q, 8p, 10, 11p, 14q, 18p Gain 1q, 7 Older age, supratentorial location, WHO grade IV Surv 0, 1, 5, 5, 10, 11, 11, 18, 18, 20, 22 months Three patients alive at 7, 24, 42 months, & one patient at 14 years Death of 11 average survival 15 months
17 Amplifier genome unfavorable 7/33 (21%) Amplifier LOH 17p Loss 10, 11p, 14 Gain 7, 1q, 6p, 8, 12, 21 Amplified genes / regions PDGFRA (4q), CCND1 (11q), CDK4 (12q), 1 with MDM4 (1q), EGFR (7p), MYC (8q), CCND2 (12p) Regions 1p36.13, 3p23p26, 5p13p12, 10q25, 11q13.5q14.1 Older age, midline location, WHO grade IV Death of 5 average survival 7.4 months; two patients alive at 7 months
18 Amplified genes Case 15 Case 10 PDGFRA CCND1 CDK4 PDGFRA 18
19 Amplified genes Case 18 Case 32 EGFR EGFR MYC CCND2 MDM4 19
20 Amplified genes / regions Case 1 Case 31 Case 5 PDGFRA 5p13.1p12 3p 1p - ARHGEF10L 20
21 Somatic mutations detected by Oncoscan microarray high confidence calls Grade III Anaplastic astrocytoma Grade Age Som mut Survival III 22 mo BRAF Alive 6+ y III 14 yr BRAF Alive ~2 y III 13 yr BRAF Alive 13 y III 15 yr EGFR Alive 7 mo III 5 yr EGFR Alive 7 mo III 12 yr TP53, IDH1 Alive 9 yr Grade IV - Glioblastoma Grade Age Som mut Survival IV 5 yr EGFR 9 mo IV 8 yr EGFR 1 mo IV 8 yr EGFR 11 mo IV 15 mo TP53 4 mo IV 10 yr TP53 1 mo IV 10 yr TP53 5 mo IV 12 yr TP53 Alive 7mo IV 13 yr TP53 11 mo IV 14 yr TP53, IDH1 18 mo IV 14 yr TP53 10 mo
22 Methylation profiling has identified 6 epigenetically distinct subgroups of GBM Methylation K27 G34 IDH RTK-1 Mesenchymal PXA-like Age Young child Adolescent YA Adult YA All Adolescent YA Young child location Recurrent oncogenic drivers Approx med survival Midline, infratentorial H3 K27, TP53 ATRX PDGFRA ACVR1 FGFR1 mutations Supratentorial Supratentorial Supratentorial Supratentorial supratentorial H3 G34, TP53, ATRX mutations IDH1 or IDH2, TP53, ATRX mutations PDGFRA amp, TP53 mut, CDKN2A/B del, EGFR amp NF1, TP53 mutations CDKN2A/B del EGFR amp PDGFRA amp BRAF V600E CDKN2A del 6 months 1 year > 2 years 1 year 1 year >4 years Expression Proneural Mixed Proneural Proneural Mesenchymal Unknown Modified from Figure 2, Gajjar, J Clin Oncol 2015
23 Tumor site 4/9 midline tumors H3 K27M mutated Sex Age Grd H3 K27M 17p TP53 Thalamus M 10 y IV Pos LOH mut Other Amplified PDGFRA; triploid Survival 1 mo Thalamus F 12 y IV Pos LOH 6q, 10q, 14 loss, hmz PTEN loss 0 mo Thalamus F 5 y III Pos LOH Amplified 3p22p26, 5p12p13.1; +2,+7,-10 alive 7mo Pons F 5 y IV Pos Loss 1q gain; 10q loss; hypodiploid 5 mo Thalamus M 15 y III Neg -- amplified MDM4, EGFR, MYC, CCND2; 9p, 14 loss; 12p gain alive 7 mo Basal ganglia M 4 y III Neg -- ROS1-GOPC deletion fusion alive 17 m Thalamus F 8 y IV Neg -- 1q, 12p gain; 6q, 9p, 10 loss 1 mo Basal ganglia F 6 m III Neg -- ROS1-GOPC deletion fusion 5 mo Thalamus F 5 y IV Neg LOH Amplified EGFR; 1q gain; 6q, 10, 14 loss 9 mo
24 Survival - age 24
25 Survival - tumor location
26 Survival WHO Grade III vs Grade IV
27 Ongoing study Further analysis Correlate clinical characteristics and additional pathologic characteristics with the genomic data Additional somatic mutation analysis If possible, whole exome sequencing Collaboration with other pediatric institutions 27
28 Collaborators Melissa Gener Kevin Ginn Lei Zhang Elena Repnikova John Herriges Midhat Farooqi Vincent Staggs Eugenio Taboada Jessica Nick Tara Bendorf Scott Smith Robin Ryan Stephanie Fiedler Kris Lawrence Children s Mercy Cancer Center 28
Gliomas in the 2016 WHO Classification of CNS Tumors
Gliomas in the 2016 WHO Classification of CNS Tumors Hindi N Al-Hindi, MD, FCAP Consultant Neuropathologist and Head Section of Anatomic Pathology Department of Pathology and Laboratory Medicine King Faisal
More informationNeuropathology Evening Session: Case 3
Neuropathology Evening Session: Case 3 Christine E. Fuller, MD Cincinnati Children s Hospital Medical Center Disclosure of Relevant Financial Relationships USCAP requires that all faculty in a position
More informationCopy number and somatic mutations drive tumors
Detection of copy number alterations, ploidy and loss of heterozygosity across the genome in FFPE specimens Utility for diagnosis and treatment with comparison to FISH-based and as a complement to sequencing
More informationClassification of Diffuse Gliomas: Progress, Pearls and Pitfalls. Rob Macaulay Neuropathologist, MCC October 21, 2017
Classification of Diffuse Gliomas: Progress, Pearls and Pitfalls Rob Macaulay Neuropathologist, MCC October 21, 2017 Objectives Explain why the designation high grade glioma is preferable to GBM for intraoperative
More informationMolecular Genetics of Paediatric Tumours. Gino Somers MBBS, BMedSci, PhD, FRCPA Pathologist-in-Chief Hospital for Sick Children, Toronto, ON, CANADA
Molecular Genetics of Paediatric Tumours Gino Somers MBBS, BMedSci, PhD, FRCPA Pathologist-in-Chief Hospital for Sick Children, Toronto, ON, CANADA Financial Disclosure NanoString - conference costs for
More informationNature Genetics: doi: /ng.2995
Supplementary Figure 1 Kaplan-Meier survival curves of patients with brainstem tumors. (a) Comparison of patients with PPM1D mutation versus wild-type PPM1D. (b) Comparison of patients with PPM1D mutation
More informationAssessment of Breast Cancer with Borderline HER2 Status Using MIP Microarray
Assessment of Breast Cancer with Borderline HER2 Status Using MIP Microarray Hui Chen, Aysegul A Sahin, Xinyan Lu, Lei Huo, Rajesh R Singh, Ronald Abraham, Shumaila Virani, Bal Mukund Mishra, Russell Broaddus,
More informationKarl Kashofer, Phd Institut für Pathologie Medizinische Universität Graz
Expanding on WHO guideline compliant molecular testing of central nervous system tumors by low density whole genome sequencing. Karl Kashofer, Phd Institut für Pathologie Medizinische Universität Graz
More informationA clinical perspective on neuropathology and molecular genetics in brain tumors
A clinical perspective on neuropathology and molecular genetics in brain tumors M.J. van den Bent Erasmus MC Cancer Institute Rotterdam, the Netherlands Disclosures Member speakersbureau: MSD Consultancy:
More informationMOLECULAR DIAGNOSTICS OF GLIOMAS
MOLECULAR DIAGNOSTICS OF GLIOMAS Arie Perry, M.D. Director, Neuropathology Division DIFFUSE GLIOMAS Cell types Astrocytomas (A) Oligodendrogliomas (O) Mixed oligoastrocytoma (MOA) Three WHO grades: II,
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups
More informationThe Cancer Genome Atlas Research Network* abstract
The new england journal of medicine established in 1812 June 25, 2015 vol. 372 no. 26 Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas The Cancer Genome Atlas Research Network*
More informationClinical significance of genetic analysis in glioblastoma treatment
Clinical significance of genetic analysis in glioblastoma treatment Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Koji Yoshimoto Can we get prognostic
More informationJennifer Hauenstein Oncology Cytogenetics Emory University Hospital Atlanta, GA
Comparison of Genomic Coverage using Affymetrix OncoScan Array and Illumina TruSight Tumor 170 NGS Panel for Detection of Copy Number Abnormalities in Clinical GBM Specimens Jennifer Hauenstein Oncology
More informationWhole Genome and Transcriptome Analysis of Anaplastic Meningioma. Patrick Tarpey Cancer Genome Project Wellcome Trust Sanger Institute
Whole Genome and Transcriptome Analysis of Anaplastic Meningioma Patrick Tarpey Cancer Genome Project Wellcome Trust Sanger Institute Outline Anaplastic meningioma compared to other cancers Whole genomes
More informationDiagnostic application of SNParrays to brain cancers
Diagnostic application of SNParrays to brain cancers Adriana Olar 4/17/2018 No disclosures 55 yo M, focal motor seizure T2 T1-post C DIAGNOSIS BRAIN, LEFT FRONTAL LOBE, BIOPSY: - DIFFUSE GLIOMA, OLIGODENDROGLIAL
More informationBRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma
BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma by Matthew R. Mistry A thesis submitted in conformity with the requirements for the degree
More informationEnterprise Interest None
Enterprise Interest None Heterogeneous chromosomal profiles in a unique series of DIPG in children and young adults European Congress of Pathology Amsterdam, 6 th September 2017 Charlotte Dufour, Romain
More informationThe mutations that drive cancer. Paul Edwards. Department of Pathology and Cancer Research UK Cambridge Institute, University of Cambridge
The mutations that drive cancer Paul Edwards Department of Pathology and Cancer Research UK Cambridge Institute, University of Cambridge Previously on Cancer... hereditary predisposition Normal Cell Slightly
More informationApplication of Whole Genome Microarrays in Cancer: You should be doing this test!!
Application of Whole Genome Microarrays in Cancer: You should be doing this test!! Daynna Wolff, Ph.D. Director, Cytogenetics and Genomics Disclosures Clinical Laboratory Director and Employee, Medical
More informationPLEASE STAND BY the webinar Unearthing Hidden Genomic Data in Solid Tumor Samples: Are Your FFPE Samples Revealing All? will begin shortly
Science Webinar Series PLEASE STAND BY the webinar Unearthing Hidden Genomic Data in Solid Tumor Samples: Are Your FFPE Samples Revealing All? will begin shortly Change the size of any window by dragging
More informationCharacterisation of structural variation in breast. cancer genomes using paired-end sequencing on. the Illumina Genome Analyser
Characterisation of structural variation in breast cancer genomes using paired-end sequencing on the Illumina Genome Analyser Phil Stephens Cancer Genome Project Why is it important to study cancer? Why
More informationThe Role of ploidy in neuroblastoma. Michael D. Hogarty, MD Division of Oncology Children s Hospital of Philadelphia
The Role of ploidy in neuroblastoma Reprinted from NB Journal Summer Issue 2003 Children s Neuroblastoma Cancer Foundation Michael D. Hogarty, MD Division of Oncology Children s Hospital of Philadelphia
More informationSALSA MLPA probemix P175-A3 Tumour Gain Lot A3-0714: As compared to the previous version A2 (lot A2-0411), nine probes have a small change in length.
SALSA MLPA probemix P175-A3 Tumour Gain Lot A3-0714: As compared to the previous version A2 (lot A2-0411), nine probes have a small change in length. This SALSA probemix is for basic research only! This
More informationThe New WHO Classification and the Role of Integrated Molecular Profiling in the Diagnosis of Malignant Gliomas
The New WHO Classification and the Role of Integrated Molecular Profiling in the Diagnosis of Malignant Gliomas Stefan Prokop, MD Neuropathology Fellow Hospital of the University of Pennsylvania Background
More informationSupplemental Information. Molecular, Pathological, Radiological, and Immune. Profiling of Non-brainstem Pediatric High-Grade
Cancer Cell, Volume 33 Supplemental Information Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial Alan Mackay,
More informationNext Generation Sequencing in Clinical Practice: Impact on Therapeutic Decision Making
Next Generation Sequencing in Clinical Practice: Impact on Therapeutic Decision Making November 20, 2014 Capturing Value in Next Generation Sequencing Symposium Douglas Johnson MD, MSCI Vanderbilt-Ingram
More informationCynthia Hawkins. Division of Pathology, Labatt Brain Tumour Research Centre, The Hospital for Sick Children, University of Toronto, Canada
Cynthia Hawkins Division of Pathology, Labatt Brain Tumour Research Centre, The Hospital for Sick Children, University of Toronto, Canada To apply a practical diagnostic approach to pediatric high grade
More informationMolecular diagnostics of gliomas: state of the art
Acta Neuropathol (2010) 120:567 584 DOI 10.1007/s00401-010-0736-4 REVIEW Molecular diagnostics of gliomas: state of the art Markus J. Riemenschneider Judith W. M. Jeuken Pieter Wesseling Guido Reifenberger
More informationCurrent and future applications of Molecular Pathology. Kathy Walsh Clinical Scientist NHS Lothian
Current and future applications of Molecular Pathology Kathy Walsh Clinical Scientist NHS Lothian Molecular Pathology in Solid tumours Cancer type Genes tested Purpose Associated treatments Non small cell
More informationPr D.Figarella-Branger Service d Anatomie Pathologique et de Neuropathologie, La Timone, Marseille UMR 911 Inserm, Université d Aix-Marseille
Novelties in the WHO 2016 classification of brain tumours Pr D.Figarella-Branger Service d Anatomie Pathologique et de Neuropathologie, La Timone, Marseille UMR 911 Inserm, Université d Aix-Marseille The
More informationGlioblastoma mul,forme
Glioblastoma mul,forme Glioblastoma mul,forme (GBM), or Glioblastoma, or Grade IV Astrocytoma is the most common and most aggressive malignant primary brain tumor. GBM is usually involving glial cells,
More informationClinically Useful Next Generation Sequencing and Molecular Testing in Gliomas MacLean P. Nasrallah, MD PhD
Clinically Useful Next Generation Sequencing and Molecular Testing in Gliomas MacLean P. Nasrallah, MD PhD Neuropathology Fellow Division of Neuropathology Center for Personalized Diagnosis (CPD) Glial
More informationMorphological features and genetic alterations
Morphological features and genetic alterations Tutor : Audrey Rousseau Caget Lise: Université d Angers Iorio Vittoria: Seconda Università degli studi di Napoli Manaila Roxana: Iuliu Hatieganu University
More informationWHO 2016 CNS Tumor Classification Update. DISCLOSURES (Arie Perry, MD) PATTERN RECOGNITION. Arie Perry, M.D. Director, Neuropathology
WHO 2016 CNS Tumor Classification Update Arie Perry, M.D. Director, Neuropathology DISCLOSURES (Arie Perry, MD) I have no financial relationships to disclose. - and - I will not discuss off label use or
More informationDevelopments in small cell lung cancer G. Giaccone, MD PhD Chief, Medical Oncology Branch and Affiliates National Cancer Institute Bethesda MD USA
Developments in small cell lung cancer G. Giaccone, MD PhD Chief, Medical Oncology Branch and Affiliates National Cancer Institute Bethesda MD USA Geneva April 20, 2012 Neuroendocrine tumors of lung Typical
More informationPrecision medicine for gliomas
Precision medicine for YAZMIN ODIA, MD MS LEAD PHYSICIAN OF MEDICAL NEURO-ONCOLOGY DISCLOSURES Novocure: Advisory Board for Optune in No other financial conflicts of interest Glioma OVERVIEW INFILTRATIVE,
More informationThe role of cytogenomics in the diagnostic work-up of Chronic Lymphocytic Leukaemia
The role of cytogenomics in the diagnostic work-up of Chronic Lymphocytic Leukaemia Adrian Zordan, Meaghan Wall, Ruth MacKinnon, Pina D Achille & Lynda Campbell Victorian Cancer Cytogenetics Service (VCCS)
More informationRadioterapia no Tratamento dos Gliomas de Baixo Grau
Radioterapia no Tratamento dos Gliomas de Baixo Grau Dr. Luis Souhami University Montreal - Canada Low Grade Gliomas Relatively rare Heterogeneous, slow growing tumors WHO Classification Grade I Pilocytic
More information2017 Diagnostic Slide Session Case 3
2017 Diagnostic Slide Session Case 3 Andrew Gao, MD Lili-Naz Hazrati, MD, PhD Cynthia Hawkins, MD, PhD Hospital for Sick Children and University of Toronto, Toronto, Canada Disclosures: none Clinical History
More information5 th July 2016 ACGS Dr Michelle Wood Laboratory Genetics, Cardiff
5 th July 2016 ACGS Dr Michelle Wood Laboratory Genetics, Cardiff National molecular screening of patients with lung cancer for a national trial of multiple novel agents. 2000 NSCLC patients/year (late
More informationApplications of molecular neuro-oncology - a review of diffuse glioma integrated diagnosis and emerging molecular entities
Wood et al. Diagnostic Pathology (2019) 14:29 https://doi.org/10.1186/s13000-019-0802-8 REVIEW Applications of molecular neuro-oncology - a review of diffuse glioma integrated diagnosis and emerging molecular
More informationWhat yield in the last decade about Molecular Diagnostics in Neuro
What yield in the last decade about Molecular Diagnostics in Neuro Oncology? Raphael Salles S.Medeiros Neuropathologist at HC FMUSP Clinical Research Project Manager at Oncology department at Hospital
More informationDisclosures Genomic testing in lung cancer
Disclosures Genomic testing in lung cancer No disclosures Objectives Understand how FISH and NGS provide complementary data for the evaluation of lung cancer Recognize the challenges of performing testing
More informationIntegrated Analysis of Copy Number and Gene Expression
Integrated Analysis of Copy Number and Gene Expression Nexus Copy Number provides user-friendly interface and functionalities to integrate copy number analysis with gene expression results for the purpose
More informationPI3-Kinase Signaling. Rational Incorporation of Novel Agents into Multimodality Therapy. PI3-kinase. PI3-kinase 5/2/2010
Rational Incorporation of Novel Agents into Multimodality Therapy I3-Kinase Signaling EGF IRS1 I3K EGFR I2 I3 TEN Rictor GßL AKT RAS40 Survival Raptor GßL Daphne Haas-Kogan UCSF Annual Course April 30-May
More informationHematopathology Service Memorial Sloan Kettering Cancer Center, New York
SH2017-0334 t(14;18) Negative Follicular Lymphoma with 1p36 abnormality associated with In Situ Follicular Neoplasia with t(14;18) translocation Pallavi Khattar MD, Jennifer Maerki MD, Alexander Chan MD,
More informationIDH1 R132H/ATRX Immunohistochemical validation
IDH1 R132H/ATRX Immunohistochemical validation CIQC/DSM 2016 12 June 2016 0835-0905 Stephen Yip, M.D., Ph.D., FRCPC University of British Columbia Disclosure Statement I have nothing to disclose I will
More informationSupplementary Figure 1. Copy Number Alterations TP53 Mutation Type. C-class TP53 WT. TP53 mut. Nature Genetics: doi: /ng.
Supplementary Figure a Copy Number Alterations in M-class b TP53 Mutation Type Recurrent Copy Number Alterations 8 6 4 2 TP53 WT TP53 mut TP53-mutated samples (%) 7 6 5 4 3 2 Missense Truncating M-class
More informationDisclaimers. Molecular pathology of brain tumors. Some aspects only. Some details are inevitably personal opinions
Molecular pathology of brain tumors Disclaimers Some aspects only H.K. Ng The Chinese University of Hong Kong Some details are inevitably personal opinions Free ppt : http://www.acp.cuhk.edu.hk/hkng Why
More informationTumours of the Central Nervous System (CNS) Molecular Information Reporting Guide
Sponsored by Tumours of the Central Nervous System (CNS) Molecular Information Reporting Guide Family/Last name Given name(s) Date of birth DD MM YYYY Patient identifiers Date of request Accession/Laboratory
More informationSystemic Treatment. Third International Neuro-Oncology Course. 23 May 2014
Low-Grade Astrocytoma of the CNS: Systemic Treatment Third International Neuro-Oncology Course São Paulo, Brazil 23 May 2014 John de Groot, MD Associate Professor, Neuro-Oncology UT MD Anderson Cancer
More informationTumors of the Nervous System
Tumors of the Nervous System Peter Canoll MD. PhD. What I want to cover What are the most common types of brain tumors? Who gets them? How do they present? What do they look like? How do they behave? 1
More informationCNS pathology Third year medical students. Dr Heyam Awad 2018 Lecture 12: CNS tumours 2/3
CNS pathology Third year medical students Dr Heyam Awad 2018 Lecture 12: CNS tumours 2/3 Pilocytic astrocytoma Relatively benign ( WHO grade 1) Occurs in children and young adults Mostly: in the cerebellum
More informationCase Presentation: USCAP Jason T. Huse, MD, PhD Assistant Member Department of Pathology Memorial Sloan Kettering Cancer Center
Case Presentation: USCAP 2016 Jason T. Huse, MD, PhD Assistant Member Department of Pathology Memorial Sloan Kettering Cancer Center Case History 53 year old female with a long standing history of migraines
More informationOligodendroglioma: Toward Molecular Definitions in Diagnostic Neuro-Oncology
Journal of Neuropathology and Experimental Neurology Vol. 62, No. 2 Copyright 2003 by the American Association of Neuropathologists February, 2003 pp. 111 126 Oligodendroglioma: Toward Molecular Definitions
More informationBCR ABL1 like ALL: molekuliniai mechanizmai ir klinikinė reikšmė. IKAROS delecija: molekulinė biologija, prognostinė reikšmė. ASH 2015 naujienos
BCR ABL1 like ALL: molekuliniai mechanizmai ir klinikinė reikšmė. IKAROS delecija: molekulinė biologija, prognostinė reikšmė. ASH 2015 naujienos Ph like ALL BCR ABL1 like acute lymphoblastic leukemia (ALL)
More informationGenomic instability. Amin Mahpour
Genomic instability Amin Mahpour 1 Some questions to ponder What is Genomic instability? What factors contribute to the genomic integrity? How we identify these aberrations? 2 PART I: MOLECULAR BIOLOGY
More informationGenomic complexity and arrays in CLL. Gian Matteo Rigolin, MD, PhD St. Anna University Hospital Ferrara, Italy
Genomic complexity and arrays in CLL Gian Matteo Rigolin, MD, PhD St. Anna University Hospital Ferrara, Italy Clinical relevance of genomic complexity (GC) in CLL GC has been identified as a critical negative
More informationCorporate Medical Policy
Corporate Medical Policy Analysis of MGMT Promoter Methylation in Malignant Gliomas File Name: Origination: Last CAP Review: Next CAP Review: Last Review: analysis_of_mgmt_promoter_methylation_in_malignant_gliomas
More informationCytogenetics 101: Clinical Research and Molecular Genetic Technologies
Cytogenetics 101: Clinical Research and Molecular Genetic Technologies Topics for Today s Presentation 1 Classical vs Molecular Cytogenetics 2 What acgh? 3 What is FISH? 4 What is NGS? 5 How can these
More informationWHO 2016 CNS TUMOR CLASSIFICATION UPDATE. Arie Perry, M.D. Director, Neuropathology
WHO 2016 CNS TUMOR CLASSIFICATION UPDATE Arie Perry, M.D. Director, Neuropathology DISCLOSURES (Arie Perry, MD) I have no financial relationships to disclose. - and - I will not discuss off label use or
More informationLooking Beyond the Standard-of- Care : The Clinical Trial Option
1 Looking Beyond the Standard-of- Care : The Clinical Trial Option Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor
More informationH3F3A K27M Mutation in Pediatric CNS Tumors. A Marker for Diffuse High-Grade Astrocytomas
Anatomic Pathology / H3.3 Mutations in Pediatric Diffuse High-Grade Astrocytomas H3F3A K27M Mutation in Pediatric CNS Tumors A Marker for Diffuse High-Grade Astrocytomas Gerrit H. Gielen, MD, 1 Marco Gessi,
More informationClinical Grade Genomic Profiling: The Time Has Come
Clinical Grade Genomic Profiling: The Time Has Come Gary Palmer, MD, JD, MBA, MPH Senior Vice President, Medical Affairs Foundation Medicine, Inc. Oct. 22, 2013 1 Why We Are Here A Shared Vision At Foundation
More informationGenomic Medicine: What every pathologist needs to know
Genomic Medicine: What every pathologist needs to know Stephen P. Ethier, Ph.D. Professor, Department of Pathology and Laboratory Medicine, MUSC Director, MUSC Center for Genomic Medicine Genomics and
More informationMolecular Markers. Marcie Riches, MD, MS Associate Professor University of North Carolina Scientific Director, Infection and Immune Reconstitution WC
Molecular Markers Marcie Riches, MD, MS Associate Professor University of North Carolina Scientific Director, Infection and Immune Reconstitution WC Overview Testing methods Rationale for molecular testing
More informationSYSTEMIC MANAGEMENT OF PEDIATRIC PRIMARY BRAIN TUMORS
SYSTEMIC MANAGEMENT OF PEDIATRIC PRIMARY BRAIN TUMORS María E. Echevarría, MD Assistant Professor University of Puerto Rico Medical Sciences Campus DISCLOSURES No disclosures INTRODUCTION Pediatric CNS
More informationMolecular prognostic factors in glioblastoma: state of the art and future challenges. Author Proof
Review Molecular prognostic factors in glioblastoma: state of the art and future challenges Ana Xavier-Magalhães 1,2, Meera Nandhabalan 3,4, Chris Jones 3,4 & Bruno M Costa* 1,2 Practice Points Glioblastoma
More informationPharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma
Supplementary information for: Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma Rintaro Hashizume 1, Noemi Andor 2, Yuichiro Ihara 2, Robin Lerner 2, Haiyun
More informationSALSA MLPA probemix P315-B1 EGFR
SALSA MLPA probemix P315-B1 EGFR Lot B1-0215 and B1-0112. As compared to the previous A1 version (lot 0208), two mutation-specific probes for the EGFR mutations L858R and T709M as well as one additional
More information10/2/17. MELTUMP, SAMPUS, AST.An Algorithmic Approach to Challenging (Often Borderline) Melanocytic Tumors. An Introduction to SNP Arrays
MELTUMP, SAMPUS, AST.An Algorithmic Approach to Challenging (Often ) Melanocytic Tumors An Introduction to SNP Arrays Rajiv M. Patel, M.D. RCPA NZ ASM 2017 (11:45-12:30pm, Saturday, 23-09-17) Why do we
More informationMRC-Holland MLPA. Description version 05; 03 April 2019
SALSA MLPA probemix ME012-A1 MGMT-IDH1-IDH2 Lot A1-1215. Glioblastoma, the most common malignant primary brain tumour, is characterised by aggressive behaviour and a poor survival. Hypermethylation in
More informationSureSelect Cancer All-In-One Custom and Catalog NGS Assays
SureSelect Cancer All-In-One Custom and Catalog NGS Assays Detect all cancer-relevant variants in a single SureSelect assay SNV Indel TL SNV Indel TL Single DNA input Single AIO assay Single data analysis
More informationComputer Science, Biology, and Biomedical Informatics (CoSBBI) Outline. Molecular Biology of Cancer AND. Goals/Expectations. David Boone 7/1/2015
Goals/Expectations Computer Science, Biology, and Biomedical (CoSBBI) We want to excite you about the world of computer science, biology, and biomedical informatics. Experience what it is like to be a
More informationNature Genetics: doi: /ng Supplementary Figure 1. Depths and coverages in whole-exome and targeted deep sequencing data.
Supplementary Figure 1 Depths and coverages in whole-exome and targeted deep sequencing data. Depth (top) and coverage (bottom) of whole-exome sequencing for 38 independent JPN cases (mean depth = 130)
More informationUpdate on Spitzoid and Blue nevus-like melanocytic lesions Emphasis on molecular studies informing diagnosis, prognosis and therapy
Update on Spitzoid and Blue nevus-like melanocytic lesions Emphasis on molecular studies informing diagnosis, prognosis and therapy Michael T. Tetzlaff MD, PhD Associate Professor Department of Pathology,
More informationMolecular Markers in Acute Leukemia. Dr Muhd Zanapiah Zakaria Hospital Ampang
Molecular Markers in Acute Leukemia Dr Muhd Zanapiah Zakaria Hospital Ampang Molecular Markers Useful at diagnosis Classify groups and prognosis Development of more specific therapies Application of risk-adjusted
More informationpatients in the era of
Communicating with cancer patients in the era of personalized medicine September 9 th, 2017 Gerald Prager, M.D. Comprehensive Cancer Center Vienna Medical University of Vienna, Austria Gerald Prager, M.D.
More informationDo acgh analysis have a place in routine cytogenetic workup in leukemia/cancer? - A single institution experience. Cambridge, April 9 th 2013
Do acgh analysis have a place in routine cytogenetic workup in leukemia/cancer? - A single institution experience. Cambridge, April 9 th 2013 Aarhus University Hospital Eigil Kjeldsen, Cancercytogenetic
More informationCelebrating 20 years of the Database Joint UKCCG and CHO Annual Conference. 22 nd -23 rd March 2012 Newcastle upon Tyne
Celebrating 20 years of the Database Joint UKCCG and CHO Annual Conference 22 nd -23 rd March 2012 Newcastle upon Tyne The following years. FISH and genomics Christine Harrison Chair, UK Cancer Cytogenetics
More informationMolecular pathology of paediatric central nervous system tumours
Journal of Pathology J Pathol 2017; 241: 159 172 Published online 10 November 2016 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/path.4813 INVITED REVIEW Molecular pathology of paediatric
More informationMolecular Testing in Lung Cancer
Molecular Testing in Lung Cancer Pimpin Incharoen, M.D. Assistant Professor, Thoracic Pathology Department of Pathology, Ramathibodi Hospital Genetic alterations in lung cancer Source: Khono et al, Trans
More informationAddressing the challenges of genomic characterization of hematologic malignancies using microarrays
Addressing the challenges of genomic characterization of hematologic malignancies using microarrays Sarah South, PhD, FACMG Medical Director, ARUP Laboratories Department of Pediatrics and Pathology University
More informationGenomic Methods in Cancer Epigenetic Dysregulation
Genomic Methods in Cancer Epigenetic Dysregulation Clara, Lyon 2018 Jacek Majewski, Associate Professor Department of Human Genetics, McGill University Montreal, Canada A few words about my lab Genomics
More informationDNA methylation signatures for 2016 WHO classification subtypes of diffuse gliomas
Paul et al. Clinical Epigenetics (2017) 9:32 DOI 10.1186/s13148-017-0331-9 RESEARCH Open Access DNA methylation signatures for 2016 WHO classification subtypes of diffuse gliomas Yashna Paul, Baisakhi
More informationGeneral: Brain tumors are lesions that have mass effect distorting the normal tissue and often result in increased intracranial pressure.
1 Lecture Objectives Know the histologic features of the most common tumors of the CNS. Know the differences in behavior of the different tumor types. Be aware of the treatment modalities in the various
More informationJ Clin Oncol 29: by American Society of Clinical Oncology INTRODUCTION
VOLUME 29 NUMBER 3 OCTOBER 2 211 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Barbara S. Paugh, Alberto Broniscer, Chunxu Qu, Claudia P. Miller, Junyuan Zhang, Ruth G. Tatevossian, Arzu Onar-
More informationObjectives. Morphology and IHC. Flow and Cyto FISH. Testing for Heme Malignancies 3/20/2013
Molecular Markers in Hematologic Malignancy: Ways to locate the needle in the haystack. Objectives Review the types of testing for hematologic malignancies Understand rationale for molecular testing Marcie
More informationPROCARBAZINE, lomustine, and vincristine (PCV) is
RAPID PUBLICATION Procarbazine, Lomustine, and Vincristine () Chemotherapy for Anaplastic Astrocytoma: A Retrospective Review of Radiation Therapy Oncology Group Protocols Comparing Survival With Carmustine
More informationAdvances in Brain Tumor Research: Leveraging BIG data for BIG discoveries
Advances in Brain Tumor Research: Leveraging BIG data for BIG discoveries Jill Barnholtz-Sloan, PhD Associate Professor & Associate Director for Bioinformatics and Translational Informatics jsb42@case.edu
More informationPeter Canoll MD. PhD.
Tumors of the Nervous System Peter Canoll MD. PhD. What I want to cover What are the most common types of brain tumors? Who gets them? How do they ypresent? What do they look like? How do they behave?
More informationChromosomal Aberrations
Chromosomal Aberrations Chromosomal Aberrations Abnormalities of chromosomes may be either numerical or structural and may involve one or more autosomes, sex chromosomes, or both simultaneously. Numerical
More informationSynovial Sarcoma. Dr. Michelle Ghert Dr. Rajiv Gandhi
Synovial Sarcoma Dr. Michelle Ghert Dr. Rajiv Gandhi Synovial Sarcoma Young adult population (15-40yrs) 5-10% of all soft tissue sarcomas mainly found in the extremities 5 year survival only 60% at presentation;
More informationIdentification and clinical detection of genetic alterations of pre-neoplastic lesions Time for the PML ome? David Sidransky MD Johns Hopkins
Identification and clinical detection of genetic alterations of pre-neoplastic lesions Time for the PML ome? David Sidransky MD Johns Hopkins February 3-5, 2016 Lansdowne Resort, Leesburg, VA Molecular
More informationNovel Oncogenic Drivers in Pediatric Gliomagenesis
University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 5-2016 Novel Oncogenic Drivers in Pediatric Gliomagenesis Alexander
More informationPersonalised cancer care Information for Medical Specialists. A new way to unlock treatment options for your patients
Personalised cancer care Information for Medical Specialists A new way to unlock treatment options for your patients Contents Optimised for clinical benefit 4 Development history 4 Full FIND IT panel vs
More informationSALSA MLPA Probemix P014-B1 Chromosome 8 Lot B and B
SALSA MLPA Probemix P014-B1 Chromosome 8 Lot B1-0916 and B1-0713. Copy number changes of the human chromosome 8 are common in many types of tumours. In most cases, losses of 8p sequences and gains of 8q
More informationNovel treatments for SCC Andrés Felipe Cardona, MD MS PhD.
Novel treatments for SCC Andrés Felipe Cardona, MD MS PhD. Clinical and Transla,onal Oncology Group Ins,tute of Oncology, Fundación Santa fe de Bogotá Clinical Epidemiology Cochrane Colombian Branch /
More informationPRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES
PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES CENTRAL NERVOUS SYSTEM ANAPLASTIC GLIOMAS CNS Site Group Anaplastic Gliomas Author: Dr. Norm Laperriere Date: February 20, 2018 1. INTRODUCTION
More information