CLINICAL UTILITY OF INTEGRATED GENOMIC PROFILING IN PEDIATRIC LEUKEMIA
|
|
|
- Dale Price
- 6 years ago
- Views:
Transcription
1 CLINICAL UTILITY OF INTEGRATED GENOMIC PROFILING IN PEDIATRIC LEUKEMIA FUMIN LIN, Ph.D. CANCER GENOMIC DIAGNOSTIC LABORATORY DIVISION OF GENOMIC DIAGNOSTICS 1
2 PEDIATRIC LEUKEMIA Common types of leukemia in children: Acute lymphoblastic leukemia (ALL) Acute myelogenous leukemia (AML) Juvenile myelomonocytic leukemia (JMML) Leukemia is the most common cancer in children: Accounts for one third of pediatric cancer Affects approximately 4,000 children each year in the U.S. Biologically diverse diseases containing various genomic alternations including SNVs, indels, CNVs and gene fusion 2
3 COMPREHENSIVE HEME PANEL AT CHOP Patient samples (blood, bone marrow or FFPE) Heme panel (Agilent): 99 Leukemia-related cancer genes 2 leukemia drug toxicity genes TAT: 3 weeks DNA isolation and Heme panel library construction 1 st and 2 nd review RNA isolation and Fusion panel library construction 1 st and 2 nd review Fusion panel (Archer): 106 major fusion partner genes 586 known fusions and novel ones TAT: 1-3 weeks GC review Director report sign out 3
4 LEUKEMIA CASES SINCE JAN Heme cases: 73% comprehensive, 23% heme only and 4% fusion only Clinically significant variants are identified in 87% of cases result case percentage Tier1/2 (clinically significant) % Tier3 (VOUS) % Tier4 (rare benign) % ALL AML JMML CML others Number Percentage 69.38% 20.00% 3.75% 0.63% 6.25% [CATEG ORY NAME] 9% Tier4 (rare benign) [PERCE NTAGE] Tier1/2 (clinical ly significa nt 87% CML JMML 1% 4% AML 20% others 6% ALL 69% 4
5 RESULTS: SNV&INDEL 178 clinically significant SNVs or Indels (65% positive) 61 genes Gene time Frequency NRAS % KRAS % NOTCH % RUNX % TP % WT % PTPN % CREBBP % FLT % JAK % PAX % MPL % NF % Cancer-related Variant time Frequency NRAS c.38g>a % KRAS c.436g>a % NRAS c.35g>a % JAK2 c.2047a>g % KRAS c.35g>a % KRAS c.35g>c % KRAS c.38g>a % NRAS c.182a>g % NRAS c.37g>c % TP53 c.789_833delinsccct % WHSC1 c.3295g>a % Drug (Mercaptopurine) Toxicity Variant time Frequency TPMT c.719a>g % TPMT c.460g>a % NUDT15 c.415c>t % 5
6 RESULTS: SNV & INDEL ALL: 115 SNV/Indel identified in 38 genes (64% positive; enriched with KRAS, NOTCH1, PAX5 and PTPN11 variants) AML: 59 SNV/Indel identified in 37 genes (75% positive; enriched with RUNX1 variants) NRAS and TP53 are frequently mutated in both. NRAS c.38g>a found in both. ALL Gene time frequency KRAS % NOTCH % NRAS % TP % PAX % CREBBP % PTPN % JAK % Variant time frequency KRAS c.436g>a % NRAS c.35g>a % NRAS c.38g>a % KRAS c.35g>a % KRAS c.38g>a % NRAS c.182a>g % JAK2 c.2047a>g % TP53 c.789_833delinsccct % WHSC1 c.3295g>a % AML Gene time frequency RUNX % ASXL % FLT % NRAS % TP % Variant time frequency NRAS c.38g>a % RUNX1 c.247_248insgga % TERT c.-124c>a % 6
7 >400 clinically significant CNVs reported (67.5% positive) CNV time frequency loss/loh of 9p (CDKN2A/B) % gain of chr % RESULTS: CNV loss/loh of 19p (TCF3) 10% gain of 17q (IKZF3) 10% loss/loh of 17p (TP53) 7% [CATEGORY NAME] 30% loss/loh of 9p (PAX5) % loss/loh of 7p (IKZF1) % loss/loh of 19p (TCF3) % loss/loh of 7p (IKZF1) 11% [CATEGORY NAME] 18% gain of 17q (IKZF3) % loss/loh of 17p (TP53) % loss/loh of 9p (PAX5) 12% 7
8 RESULTS: CNV ALL: 74% positive AML: 69% positive Distinct CNV patterns between ALL and AML ALL CNV present times frequency loss/loh of 9p (CDKN2A/B) % gain of chr % loss/loh of 9p (PAX5) % gain of 17q (IKZF3) % loss/loh of 7p (IKZF1) % loss/loh of 19p (TCF3) % loss/loh of 17p (TP53) % AML CNV present times frequency gain of chr % loss of chr % 8
9 RESULTS: FUSION 25 fusions identified in 43 patients (27% positive) 20 known fusions and 5 novel ones(*) Fusion 5' partner 3' partner time frequency ETV6-RUNX % TCF3-? TCF3 PBX1, HLF % KMT2A-? KMT2A MLLT3, MLLT1, MLLT10, MAML % PAX5-? PAX5 SOX5*, MBNL1*, JAK2, DACH1, AHCYL2* %?-CRLF2 P2RY8, IGH CRLF %?-ABL1 NUP214, BCR ABL % TBL1XR1-PIK3CA % SEC16A-NOTCH % RUNX1-RUNX1T % PML-RARA % NUP98-KDM5A % FUS-ERG % EPOR-IGH % VIM-ALK* % EWSR1-HLF* % 9
10 RESULTS: FUSION ALL: 21 fusions found in 38 cases (34%) AML: 4 fusions found in 5 cases (16%) ALL AML Fusion in ALL 5' partner 3' partner time frequency ETV6-RUNX % TCF3-? TCF3 PBX1, HLF % Fusion in AML time frequency KMT2A-MLLT % NUP98-KDM5A % PAX5-? PAX5 SOX5*, MBNL1*, JAK2, DACH1, AHCYL2* % RUNX1-RUNX1T % KMT2A-? KMT2A MLLT3, MLLT1, MAML %?-CRLF2 P2RY8, IGH CRLF %?-ABL1 NUP214, BCR ABL % PML-RARA % 10
11 IMPACT ON DIAGNOSIS, PROGNOSIS AND THERAPY Change/specify diagnosis Pancytopenia ALL Concern for leukemia JMML Treatment suggestion BCR-ABL1 ALL; CRLF2-, JAK2-, ABL1-associated fusions for Ph-like ALL KRAS, NRAS variants TPMT, NUDT15 SNPs 6-mercaptopurine intolerance Further test suggestion Germline mutation Prognosis prediction masked low-hypodiploid genomic profile POOR PROGNOSIS RUNX1-RUNX1T1 GOOD PROGNOSIS Treatment Change/specify diagnosis Further test suggestion prognosis prediction suggestion case number percentage 6.25% 21.25% 11.88% 39.38% 11
12 CASE EXAMPLE Patient: DGD HR 11 y/0 female Original diagnosis: new leukemia T-ALL? Not a typical T-ALL New diagnosis: leukemia with mixed lineage (T/Myeloid) BM morphology ~50% blasts CD3 T-cell marker positive MPO Myeloid marker dim positive 12
13 CASE EXAMPLE: SNV&INDEL Gene (gene) Transcript cdna (cnomen) Protein(pNomen) Read depth Allele Frequency WT1 NM_ c.1138delinsgg p.arg380glyfs* WT1 NM_ c.1109_1110inst p.val371fs Sanger confirmation c.1138delinsgg c.1109_1110inst 13
14 CASE EXAMPLE: CNV ABL1 amp CDKN2A/B loss cnloh Loss Gain 14
15 CASE EXAMPLE: FUSION NUP214-ABL1 15
16 CASE EXAMPLE: SUMMARY Overall findings support a leukemia of mixed lineage. Biallelic WT1 variants component of myeloid leukemia (poor prognosis) NUP214-ABL1 T-ALL (tyrosine kinase inhibitor/poor prognosis) 16
17 SUMMARY: COMPREHENSIVE HEME PANEL CLINICAL UTILITY We have studied 160 hematological malignancies using the CHOP Comprehensive Heme NGS Panel Clinically significant variants (Tier 1 and Tier 2 ) were found in 87% of cases Genomic profiling played significant part in diagnosis in 6.25% patients, prognosis in 39.38%, and therapeutic decision making in 21.25%. Potential germline/postzygotic mutations leading to cancer predisposition in 11.88% patients. Germline testing and genetic counseling were recommended for these patients 17
18 DGD Cancer Genomic Diagnostics Marilyn M. Li, M.D. Lea Surrey, M.D. Minjie Luo, Ph.D. Gerald Wertheim, M.D. Xiaonan Zhao, Ph.D. Michelle Thiess Junxia Tang, Ph.D. Kieran Pechter, Ph.D. Samuel Baker, Ph.D. Luanne Wainwright Donna Wilmoth Adam Gleason Tammy Grou Heather Krapf Nicole Blake DGD Leadership Robert Doms, M.D. Ph.D. Nancy Spinner, Ph.D. Laughlin Rice Surabhi Mulchandani Zhenming Yu, Ph.D. DGD Bioinformatics Mahdi Sarmady, Ph.D. Kajia Cao, Ph.D. Chao Wu, Ph.D. DGD GC Core Alisha Wilkens Gozde Akgumus Daniel Gallo Other DGD members CHOP Cancer Center and Pathology Dept. Steve Hunger, M.D. John Maris, M.D. Yael Mosse, M.D. Sarah Tasian, M. D. Angela Waanders, M.D. Bruce Pawel, M.D. Mariarita Santi-Vicini, M.D. Jennifer Pogoriler M.D. PhD Suzanne MacFarland M.D. And others Fengqi Chang PhD 18
BCR 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)
Out-Patient Billing CPT Codes
Out-Patient Billing CPT Codes Updated Date: August 3, 08 Client Billed Molecular Tests HPV DNA Tissue Testing 8764 No Medicare Billed - Molecular Tests NeoARRAY NeoARRAY SNP/Cytogenetic No 89 NeoLAB NeoLAB
Molecular. Oncology & Pathology. Diagnostic, Prognostic, Therapeutic, and Predisposition Tests in Precision Medicine. Liquid Biopsy.
Molecular Oncology & Pathology Hereditary Cancer Somatic Cancer Liquid Biopsy Next-Gen Sequencing qpcr Sanger Sequencing Diagnostic, Prognostic, Therapeutic, and Predisposition Tests in Precision Medicine
Case 1. Sa A.Wang, MD UT MD Anderson Cancer Center Houston, TX
Case 1 Sa A.Wang, MD UT MD Anderson Cancer Center Houston, TX Disclosure of Relevant Financial Relationships The USCAP requires that anyone in a position to influence or control the content of all CME
Initial Diagnostic Workup of Acute Leukemia
Initial Diagnostic Workup of Acute Leukemia Guideline from the College of American Pathologists (CAP) and the American Society of Hematology (ASH) Publication: Archives of Pathology and Laboratory Medicine
Acute Myeloid Leukemia with RUNX1 and Several Co-mutations
Case SH2017-0281 Acute Myeloid Leukemia with RUNX1 and Several Co-mutations James Bauer, MD, PhD David Yang, MD Erik Ranheim, MD, PhD Catherine Leith, MB, Bchir Clinical History Chief Complaint: 72 year
The Center for PERSONALIZED DIAGNOSTICS
The Center for PERSONALIZED DIAGNOSTICS Precision Diagnostics for Personalized Medicine A joint initiative between The Department of Pathology and Laboratory Medicine & The Abramson Cancer Center The (CPD)
August 17, Dear Valued Client:
August 7, 08 Re: CMS Announces 6-Month Period of Enforcement Discretion for Laboratory Date of Service Exception Policy Under the Medicare Clinical Laboratory Fee Schedule (the 4 Day Rule ) Dear Valued
Illumina Trusight Myeloid Panel validation A R FHAN R A FIQ
Illumina Trusight Myeloid Panel validation A R FHAN R A FIQ G E NETIC T E CHNOLOGIST MEDICAL G E NETICS, CARDIFF To Cover Background to the project Choice of panel Validation process Genes on panel, Protocol
Examining Genetics and Genomics of Acute Myeloid Leukemia in 2017
Examining Genetics and Genomics of Acute Myeloid Leukemia in 2017 Elli Papaemmanuil, PhD Memorial Sloan Kettering Cancer Center New York, New York, United States Today s Talk Cancer genome introduction
Blastic Plasmacytoid Dendritic Cell Neoplasm with DNMT3A and TET2 mutations (SH )
Blastic Plasmacytoid Dendritic Cell Neoplasm with DNMT3A and TET2 mutations (SH2017-0314) Habibe Kurt, Joseph D. Khoury, Carlos E. Bueso-Ramos, Jeffrey L. Jorgensen, Guilin Tang, L. Jeffrey Medeiros, and
Reporting cytogenetics Can it make sense? Daniel Weisdorf MD University of Minnesota
Reporting cytogenetics Can it make sense? Daniel Weisdorf MD University of Minnesota Reporting cytogenetics What is it? Terminology Clinical value What details are important Diagnostic Tools for Leukemia
Risk Stratification in Childhood Leukemia
Risk Stratification in Childhood Leukemia Why is risk stratification important? Toxicities Deepa Bhojwani, MD May 11, 2018 To determine intensity of therapy - When to intensify therapy - When to de-intensify
Patricia Aoun MD, MPH Professor and Vice-Chair for Clinical Affairs Medical Director, Clinical Laboratories Department of Pathology City of Hope
Patricia Aoun MD, MPH Professor and Vice-Chair for Clinical Affairs Medical Director, Clinical Laboratories Department of Pathology City of Hope National Medical Center Disclosures I have no disclosures
Update on the WHO Classification of Acute Myeloid Leukemia. Kaaren K. Reichard, MD Mayo Clinic Rochester
Update on the WHO Classification of Acute Myeloid Leukemia Kaaren K. Reichard, MD Mayo Clinic Rochester reichard.kaaren@mayo.edu Nothing to disclose Conflict of Interest Objectives Present a practical
Heme fusion assay. Valentina Nardi, MD Assistant pathologist Massachusetts General Hospital Assistant Professor Harvard Medical School
Heme fusion assay Valentina Nardi, MD Assistant pathologist Massachusetts General Hospital Assistant Professor Harvard Medical School No personal disclosures/conflicts of interest Kinase fusions in solid
Enhancing Assessment of Myeloid Disorders in the Era of Precision Medicine
Enhancing Assessment of Myeloid Disorders in the Era of Precision Medicine Michelle Afkhami, M.D. Medical Director, Clinical Molecular Diagnostic Laboratory City of Hope National Medical Center Objectives
GENETICS OF HEMATOLOGICAL MALIGNANCIES
de DUVE INSTITUTE GENETICS OF HEMATOLOGICAL MALIGNANCIES INTERUNIVERSITY CERTIFICATE IN HUMAN GENETICS Université catholique de Louvain Brussels,19/02/2016 Professor Hélène Antoine-Poirel, MD, PhD Center
Next generation sequencing analysis - A UK perspective. Nicholas Lea
Next generation sequencing analysis - A UK perspective Nicholas Lea King s HMDC LMH is part of an integrated pathology service at King s Haematological Malignancy Diagnostic Centre (HMDC) HMDC serves population
Laboratory Service Report
Client C7028846-DLP Rochester Rochester, N 55901 Specimen Type Peripheral blood CR PDF Report available at: https://test.mmlaccess.com/reports/c7028846-zwselwql7p.ashx Indication for Test DS CR Pathogenic
Next Generation Sequencing in Haematological Malignancy: A European Perspective. Wolfgang Kern, Munich Leukemia Laboratory
Next Generation Sequencing in Haematological Malignancy: A European Perspective Wolfgang Kern, Munich Leukemia Laboratory Diagnostic Methods Cytomorphology Cytogenetics Immunophenotype Histology FISH Molecular
News Release. Title Integrated molecular profiling of juvenile myelomonocytic leukemia
News Release Title Integrated molecular profiling of juvenile myelomonocytic leukemia Key Points We identified ALK/ROS1 tyrosine kinase fusions (DCTN1-ALK, RANBP2-ALK, and TBL1XR1-ROS1) in patients with
Please Silence Your Cell Phones. Thank You
Please Silence Your Cell Phones Thank You Utility of NGS and Comprehensive Genomic Profiling in Hematopathology Practice Maria E. Arcila M.D. Memorial Sloan Kettering Cancer Center New York, NY Disclosure
Celebrating 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
Test Name Results Units Bio. Ref. Interval. Positive
LL - LL-ROHINI (NATIONAL REFERENCE 135091534 Age 36 Years Gender Female 1/9/2017 120000AM 1/9/2017 105316AM 2/9/2017 104147AM Ref By Final LEUKEMIA GENETIC ROFILE ANY SIX MARKERS, CR QUALITATIVE AML ETO
Objectives. 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
Introduction of an NGS gene panel into the Haemato-Oncology MPN service
Introduction of an NGS gene panel into the Haemato-Oncology MPN service Dr. Anna Skowronska, Dr Jane Bryon, Dr Samuel Clokie, Dr Yvonne Wallis and Professor Mike Griffiths West Midlands Regional Genetics
West Midlands Regional Genetics Laboratory
West Midlands Regional Genetics Laboratory Haemato-oncology service update letter October 2017 Dear colleagues, We are writing to outline the latest developments to our service, aiming to support the management
Application 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
Laboratory Service Report
Specimen Type Peripheral blood CR PDF Report available at: https://test.mmlaccess.com/reports/c7028846-ih2xuglwpq.ashx Indication for Test DS CR Pathogenic utations Detected CR 1. JAK2: c.1849g>t;p.val617phe
We are in an era that promises a rational. treatment of cancer patients. Levy et al. Genome Research 22:2201, 2012 Vanderbilt university
Enhancing Assessment of Leukemia with Next Generation Sequencing Michelle Afkhami, M.D. Medical Director, Clinical i l Molecular l Laboratory City of Hope National Medical Center How the Expert Treat Hematologic
Molecular 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
TCF3 breakpoints of TCF3-PBX1 (patients 1a 5a) and TCF3-HLF (patients 6a 9a and11a) translocations.
Supplementary Figure 1 TCF3 breakpoints of TCF3-PBX1 (patients 1a 5a) and TCF3-HLF (patients 6a 9a and11a) translocations. The CpG motifs closest to the breakpoints are highlighted in red boxes and the
NeoTYPE Cancer Profiles
NeoTYPE Cancer Profiles Multimethod Analysis of 25+ Hematologic Diseases and Solid Tumors Anatomic Pathology FISH Molecular The next generation of diagnostic, prognostic, and therapeutic assessment NeoTYPE
Overview. Methods 9/11/2017. Next Generation Sequencing and Precision Medicine in Hematological Malignancies. Genotyping in hematology
Overview Next Generation Sequencing and Precision Medicine in Hematological Malignancies Sharathkumar Bhagavathi, MD University of Iowa Carver College of Medicine NGS as a genotyping platform in hematopathology
Jennifer 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
Test Name Results Units Bio. Ref. Interval. Positive
LL - LL-ROHINI (NATIONAL REFERENCE 135091533 Age 28 Years Gender Male 1/9/2017 120000AM 1/9/2017 105415AM 4/9/2017 23858M Ref By Final LEUKEMIA DIAGNOSTIC COMREHENSIVE ROFILE, ANY 6 MARKERS t (1;19) (q23
Molecular 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
SureSelect 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
Case #1. 65 yo man with no prior history presented with leukocytosis and circulating blasts: Bone marrow biopsy was performed
Case #1 65 yo man with no prior history presented with leukocytosis and circulating blasts: WBC 187.4K/uL ; Hgb 10.0gm/dL; Platelet 68K/uL Neutrophil % 25.0% Lymphocyte % 38.0% Monocyte % 12.0% Metamyelocyte
Molecular Advances in Hematopathology
Molecular Advances in Hematopathology HOW MOLECULAR METHODS HAVE CHANGED MY PRACTICE Objectives Understand the importance of cytogenetic/molecular studies in hematolymphoid diseases Know some of the important
Objectives and Financial Disclosure
Enhancing Assessment of Leukemia and Lymphoma with Next Generation Sequencing Michelle Afkhami, M.D. Medical Director, Clinical Molecular Laboratory Assistant Professor, Department of Pathology City of
APPLICATIONS OF NEXT GENERATION SEQUENCING IN SOLID TUMORS - PATHOLOGIST PROSPECTIVE
AMP COMPANION MEETING SYMPOSIUM AT USCAP 2015 NEXT-GENERATION OF PATHOLOGY: ROLE OF PATHOLOGIST IN NGS-BASED PERSONALIZED MEDICINE APPLICATIONS OF NEXT GENERATION SEQUENCING IN SOLID TUMORS - PATHOLOGIST
OncoKids SM Pediatric Cancer Panel
Detection of mutations and gene fusions in pediatric hematologic malignancies and solid tumors with the OncoKids SM next generation sequencing based assay Jaclyn Biegel, Timothy Triche, D. Gigi Ostrow,
AML: WHO classification, biology and prognosis. Dimitri Breems, MD, PhD Internist-Hematoloog Ziekenhuis Netwerk Antwerpen
AML: WHO classification, biology and prognosis Dimitri Breems, MD, PhD Internist-Hematoloog Ziekenhuis Netwerk Antwerpen Acute myeloid leukemia Clonal expansion of undifferentiated myeloid precursors Impaired
The Revised 2016 WHO Classification of Acute Leukemias
The Revised 2016 WHO Classification of Acute Leukemias Robert P Hasserjian, MD Associate Professor Massachusetts General Hospital and Harvard Medical School Acute leukemias Aggressive hematopoietic neoplasms
TEST MENU TEST CPT CODES TAT. Chromosome Analysis Bone Marrow x 2, 88264, x 3, Days
TEST MENU CANCER/LEUKEMIA CHROMOSOME ANALYSIS Chromosome Analysis Bone Marrow 88237 x 2, 88264, 88280 x 3, 88291 4 Days Chromosome Analysis Bone Marrow Core 88237 x 2, 88264, 88280 x 3, 88291 4 Days Chromosome
Next 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
SUPPLEMENTARY INFORMATION
Supplementary Information S1 Frequency of DNMT3A mutations in hematologic disorders and their associated clinical phenotypes. Disease Patient population Frequency (%) Associated Clinical Characteristics
Nature Medicine: doi: /nm.4439
Figure S1. Overview of the variant calling and verification process. This figure expands on Fig. 1c with details of verified variants identification in 547 additional validation samples. Somatic variants
WHO Classification of Myeloid Neoplasms with Defined Molecular Abnormalities
WHO Classification of Myeloid Neoplasms with Defined Molecular Abnormalities Robert W. McKenna, M.D. 1/2009 WHO Classification of Myeloid Neoplasms (4th Edition)--2008 Incorporates new information that
Acute leukemia and myelodysplastic syndromes
11/01/2012 Post-ASH meeting 1 Acute leukemia and myelodysplastic syndromes Peter Vandenberghe Centrum Menselijke Erfelijkheid & Afdeling Hematologie, UZ Leuven 11/01/2012 Post-ASH meeting 2 1. Acute myeloid
Addressing 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
Session 7 Summary. Magdalena Czader, MD, PhD David Czuchlewski, MD MOLECULAR GENETICS OF HEMATOPOIETIC NEOPLASMS
Session 7 Summary Magdalena Czader, MD, PhD David Czuchlewski, MD MOLECULAR GENETICS OF HEMATOPOIETIC NEOPLASMS 1 Cases according to 2016 WHO classification Acute myeloid leukemia: 26 AML with recurrent
Genomic Characterization of Acute Leukemias
Review Received: November 3, 2013 Accepted: April 10, 2014 Published online: June 20, 2014 Genomic Characterization of Acute Leukemias Sabina Chiaretti Valentina Gianfelici Giulia Ceglie Robin Foà Division
SALSA MLPA probemix P383-A1 T-ALL Lot A
SALSA MLPA probemix P383-A1 T-ALL Lot A1-0213. T-lineage acute lymphoblastic leukaemia (T-ALL) is a clonal malignant disorder of immature T-cells, which accounts for about 15% of paediatric and 25% of
NeoTYPE Cancer Profiles
NeoTYPE Cancer Profiles 30+ Multimethod Assays for Hematologic Diseases and Solid Tumors Molecular FISH Anatomic Pathology The next generation of diagnostic, prognostic, and therapeutic assessment What
A pediatric patient with acute leukemia of ambiguous lineage with a NUP98-NSD1 rearrangement SH
A pediatric patient with acute leukemia of ambiguous lineage with a NUP98NSD1 rearrangement SH20170203 Rebecca LeemanNeill, Ronald Rice, Anita Malek, Patricia Raciti, Susan Hsiao, Mahesh Mansukhani, Bachir
Changes to the Hematopoietic and Lymphoid Neoplasm Coding Manual
Changes to the Hematopoietic and Lymphoid Neoplasm Coding Manual KCR 2018 SPRING TRAINING 2018 Hematopoietic Database Updates Updates were done to the Hematopoietic Database based on the WHO Hematopoietic
JAK2 V617F analysis. Indication: monitoring of therapy
JAK2 V617F analysis BCR-ABL genotyping The exact chromosomal defect in Philadelphia chromosome is a translocation. Parts of two chromosomes, 9 and 22, switch places. The result is a fusion gene, created
The Challenges of Precision Medicine: New Advances in Molecular Diagnostic Testing- Impact for Healthcare
The Challenges of Precision Medicine: New Advances in Molecular Diagnostic Testing- Impact for Healthcare Jessica Wang-Rodriguez, MD Chief, VISN22 Consolidated Pathology and Laboratory Medicine Services
Clinical Grade Biomarkers in the Genomic Era Observations & Challenges
Clinical Grade Biomarkers in the Genomic Era Observations & Challenges IOM Committee on Policy Issues in the Clinical Development & Use of Biomarkers for Molecularly Targeted Therapies March 31-April 1,
Illumina s Cancer Research Portfolio and Dedicated Workflows
Illumina s Cancer Research Portfolio and Dedicated Workflows Michael Sohn Clinical Sales Specialist Spain&Italy 2017 2017 Illumina, Inc. All rights reserved. Illumina, 24sure, BaseSpace, BeadArray, BlueFish,
Whole 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
Enhancing Assessment of Myeloid Leukemia in the Era of Precision Medicine
Enhancing Assessment of Myeloid Leukemia in the Era of Precision Medicine Michelle Afkhami, M.D. Medical Director, Clinical Molecular Diagnostic Laboratory City of Hope National Medical Center How the
Current Techniques in Molecular Biology Friedel Nollet, Ph.D.
Current Techniques in Molecular Biology Friedel Nollet, Ph.D. Molecular Biology and Cytometry course May 16-17, 2013 Mol, SCK-CEN, Belgium Sanger DNA sequencing Kary Mullis received a Nobel Prize in chemistry
CGC myeloid malignancy working group updates. Xinjie Xu & Rashmi Kanagal-Shamanna
CGC myeloid malignancy working group updates Xinjie Xu & Rashmi Kanagal-Shamanna 8-9-2016 Group members Gordana Raca Children's Hospital Los Angeles Xinjie Xu University of Utah ARUP Laboratories Rashmi
NGS Gateway Lab Services
TM NGS Gateway Lab Services Accelerating Precision Medicine Design a Complete Genomic Testing Portfolio with Turnkey Assays About NGS Gateway Lab Services TM Designed to provide a gateway to your own in-house
5 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
Molecular Genetic Testing for the Diagnosis of Haematological Malignancies
Molecular Genetic Testing for the Diagnosis of Haematological Malignancies Dr Anthony Bench Haemto-Oncology Diagnostic Service Cambrıdge Unıversıty Hospitals NHS Foundatıon Trust Cambridge UK Molecular
Diagnostic Molecular Pathology of Myeloid Neoplasms
Diagnostic Molecular Pathology of Myeloid Neoplasms Beirut, Lebanon Tuesday November 29, 2011: Pre-congress workshop Adam Bagg University of Pennsylvania Philadelphia, USA Myeloid neoplasms Myeloproliferative
Frequency(%) KRAS G12 KRAS G13 KRAS A146 KRAS Q61 KRAS K117N PIK3CA H1047 PIK3CA E545 PIK3CA E542K PIK3CA Q546. EGFR exon19 NFS-indel EGFR L858R
Frequency(%) 1 a b ALK FS-indel ALK R1Q HRAS Q61R HRAS G13R IDH R17K IDH R14Q MET exon14 SS-indel KIT D8Y KIT L76P KIT exon11 NFS-indel SMAD4 R361 IDH1 R13 CTNNB1 S37 CTNNB1 S4 AKT1 E17K ERBB D769H ERBB
Enhancing Assessment of Myeloid Leukemia in the Era of Precision Medicine
Enhancing Assessment of Myeloid Leukemia in the Era of Precision Medicine Michelle Afkhami, M.D. Medical Director, Clinical Molecular Diagnostic Laboratory City of Hope National Medical Center How the
NUP214-ABL1 Fusion: A Novel Discovery in Acute Myelomonocytic Leukemia
Case 0094 NUP214-ABL1 Fusion: A Novel Discovery in Acute Myelomonocytic Leukemia Jessica Snider, MD Medical University of South Carolina Case Report - 64 year old Caucasian Male Past Medical History Osteoarthritis
Concomitant WT1 mutations predicted poor prognosis in CEBPA double-mutated acute myeloid leukemia
Concomitant WT1 mutations predicted poor prognosis in CEBPA double-mutated acute myeloid leukemia Feng-Ming Tien, Hsin-An Hou, Jih-Luh Tang, Yuan-Yeh Kuo, Chien-Yuan Chen, Cheng-Hong Tsai, Ming Yao, Chi-Cheng
Molecular Hematopathology Leukemias I. January 14, 2005
Molecular Hematopathology Leukemias I January 14, 2005 Chronic Myelogenous Leukemia Diagnosis requires presence of Philadelphia chromosome t(9;22)(q34;q11) translocation BCR-ABL is the result BCR on chr
HD-SNP Microarray Analysis of the Study 9 High Risk ALL Patients -
HD-SNP Microarray Analysis of the Study 9 High Risk ALL Patients - Increased Yield of Important Prognostic Information Nadine K Berry 1,2,4, Rodney J. Scott 1,4, Rosemary Sutton 5, Toby N Trahair 5, Philip
Enterprise Interest Thermo Fisher Scientific / Employee
Enterprise Interest Thermo Fisher Scientific / Employee A next-generation sequencing assay to estimate tumor mutation load from FFPE research samples Fiona Hyland. Director of R&D, Bioinformatics Clinical
Targeted Agent and Profiling Utilization Registry (TAPUR ) Study. February 2018
Targeted Agent and Profiling Utilization Registry (TAPUR ) Study February 2018 Precision Medicine Therapies designed to target the molecular alteration that aids cancer development 30 TARGET gene alterations
Genomic 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
Dr Yvonne Wallis Consultant Clinical Scientist West Midlands Regional Genetics Laboratory
Dr Yvonne Wallis Consultant Clinical Scientist West Midlands Regional Genetics Laboratory Personalised Therapy/Precision Medicine Selection of a therapeutic drug based on the presence or absence of a specific
Handout for lecture on lymphoblastic neoplasms presented by Rob McKenna
Handout for lecture on lymphoblastic neoplasms presented by Rob McKenna The following slides represent a near final version of the presentation that will be given in Maui, January 23,2018. Minor changes
New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update
Review New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update Adrián Montaño 1,, Maribel Forero-Castro 2,, Darnel Marchena-Mendoza 1,2, Rocío Benito
Comprehensive Analyses of Circulating Cell- Free Tumor DNA
Comprehensive Analyses of Circulating Cell- Free Tumor DNA Boston, MA June 28th, 2016 Derek Murphy, Ph.D. Scientist, Research and Development Personal Genome Diagnostics Acquisition of Somatic Alterations
Krishna Reddy CH and Ashwin Dalal. Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad
Clinical Cytogenetics in the Diagnosis and Prognosis of Leukemias Krishna Reddy CH and Ashwin Dalal Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad Email: krishnareddy.chr@gmail.com
Relapse Cytogenetics Overview of ALLR3 genetics Introduction to the IntReALL trial. Anthony V Moorman Leukaemia Research Cytogenetics Group
Relapse Cytogenetics Overview of ALLR3 genetics Introduction to the IntReALL trial Anthony V Moorman Leukaemia Research Cytogenetics Group Overview of ALLR3 Parker et al, Lancet 2010; 376: 2009 17 Mitoxantrone
Ph-like (BCR/ABL1-like): un apporoccio baato sul target molecolare
Ph-like (BCR/ABL1-like): un apporoccio baato sul target molecolare Sabina Chiaretti, MD PhD LE SFIDE DELLA MEDICINA DI PRECISIONE IN EMATOLOGIA Bologna 28 Giugno, 2018 Topics: BCR/ABL1-like and other subgroups
2010 Hematopoietic and Lymphoid ICD-O Codes - Alphabetical List THIS TABLE REPLACES ALL ICD-O-3 Codes
Acute basophilic leukemia 9870/3 Acute biphenotypic leukemia [OBS] 9805/3 Acute erythroid leukemia 9840/3 Acute megakaryoblastic leukemia 9910/3 Acute monoblastic and monocytic leukemia 9891/3 Acute myeloid
2012 Hematopoietic and Lymphoid ICD-O Codes - Numerical List THIS TABLE REPLACES ALL ICD-O-3 Codes
Malignant lymphoma, NOS 9590/3 Non-Hodgkin lymphoma, NOS 9591/3 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma 9596/3 Primary
Genetic Predisposition Syndromes in Myeloid Malignancies
Genetic Predisposition Syndromes in Myeloid Malignancies Lucy A. Godley, M.D., Ph.D. Section of Hematology/Oncology Departments of Medicine and Human Genetics The University of Chicago My patients and
PAX5-JAK2 fusion in acute lymphoblastic leukaemia. Dr Andrew Baldi Royal Children s Hospital 24 February 2017 Melbourne
PAX5-JAK2 fusion in acute lymphoblastic leukaemia Dr Andrew Baldi Royal Children s Hospital 24 February 2017 Melbourne Case 12-year-old girl Diagnosed with BCP ALL in November 2015 Presenting WCC 35x10
35 th UKCCG Meeting. Joint UKCCG and CHO Annual Conference. 9 th 10 th April 2013 Newcastle upon Tyne
35 th UKCCG Meeting Joint UKCCG and CHO Annual Conference 9 th 10 th April 2013 Newcastle upon Tyne Welcome! 35 th UKCCG Meeting Joint UK Cancer Cytogenetics Group and Centre Haemato-Oncology Annual Conference
Impact of Biomarkers in the Management of Patients with Acute Myeloid Leukemia
Impact of Biomarkers in the Management of Patients with Acute Myeloid Leukemia Hartmut Döhner Medical Director, Department of Internal Medicine III Director, Comprehensive Cancer Center Ulm Ulm University,
Treatments and Current Research in Leukemia. Richard A. Larson, MD University of Chicago
Treatments and Current Research in Leukemia Richard A. Larson, MD University of Chicago 2 Acute (rapid progression) Myeloid Acute myeloid leukemia (AML) Acute promyelocytic leukemia (APL) Lymphoid Acute
Lymphoblastic Leukemia / Lymphoma
1 5014 - Topics in Pediatric Hematopathology: Acute Lymphoblastic Leukemia, Including Changes in the Revised WHO Classification, and Unusual Pediatric Myeloid Neoplasms Robert W. McKenna, MD MASCP * Elizabeth
Heme 9 Myeloid neoplasms
Heme 9 Myeloid neoplasms The minimum number of blasts to diagnose acute myeloid leukemia is 5% 10% 20% 50% 80% AML with the best prognosis is AML with recurrent cytogenetic abnormality AML with myelodysplasia