“What I Do”
Download
1 / 21

“What I Do” - PowerPoint PPT Presentation


  • 90 Views
  • Uploaded on

“What I Do”. Bryan Betz PhD Clinical Assistant Professor Technical Director Molecular Diagnostics Laboratory. Molecular Diagnostics / Molecular Pathology. Application of molecular biology techniques and knowledge to clinical laboratory diagnosis. Infectious disease Inherited disease

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' “What I Do”' - eugenia-norris


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

“What I Do”

Bryan Betz PhD

Clinical Assistant Professor

Technical Director

Molecular Diagnostics Laboratory


Molecular Diagnostics / Molecular Pathology

Application of molecular biology techniques and knowledge to clinical laboratory diagnosis

  • Infectious disease

  • Inherited disease

  • Hematopathology

  • Solid Tumors

  • Identity Testing

  • Forensics

  • Pharmacogenomics

Is and will continue to revolutionize the way in which diseases are diagnosed and therapeutics are employed


Molecular Pathology

A Universal Discipline of Laboratory Medicine

INFECTIOUS

DISEASE

FORENSICS

HEMATO

PATHOLOGY

Molecular

Pathology

IDENTITY

TESTING

SOLID

TUMORS

GENETIC

DISEASE


Molecular diagnostics is a rapidly expanding field
Molecular Diagnostics is a Rapidly Expanding Field

  • Molecular diagnostics is the fastest growing segment of the diagnostics industry

  • ~$34 billion world-wide market

  • 6-8% annual growth

  • New discoveries and technology platforms are leading to the development of more and increasingly sophisticated tests

    • DNA sequencing

    • Expression microarrays

    • Array CGH

    • Detection technology/test platforms

  • Majority of the innovation and discovery takes place in Universities



Applications of Molecular Diagnostics in Clinical Laboratory Medicine

  • Infectious Disease

    • Qualitative and quantitative detection

    • Microbial identification

    • Drug resistance

  • Identity Testing

    • Determining familial relationships

    • Bone marrow engraftment analysis

    • GVHD monitoring

    • Laboratory specimen identification

    • Forensics

  • Genetics (inherited disease)

    • Diagnosis of:

      • Single gene disorders

      • Complex polygenic disorders

      • Chromosomal disorders

  • Oncology – Solid Tumor and Hematologic

    • Diagnosis

    • Prognosis

    • Predict response to therapy

    • Monitor residual disease

  • Pharmacogenomics

    • Drug metabolism

    • Determine drug dosage


UM Molecular Diagnostics Test Menu Medicine

Hematologic Malignancies

Quantitative BCR/ABL

BCR/ABL1 Kinase Mutation Analysis

FLT3 Gene Mutation

NPM1 Mutation

CEBPA Mutation

KIT D816V Mutation

t(15;17) PML/RARA Translocation

t(14;18) IGH/BCL2 Translocation

B Cell (IGH) Gene Rearrangement

T Cell Gamma (TRG) Gene Rearrangement

JAK2 V617F Mutation Detection

JAK2 Exon 12 Mutations (March 2010)

Solid Tumors

PAX/FOXO1 Translocation, Alveolar Rhabdomyosarcoma

EWSR1/WT1 Translocation, DSRT

EWS/FLI1, EWS/ERG Translocations, Ewing Sarcoma

SYT/SSX Translocation, Synovial Sarcoma

EWS/ATF1 Translocation, Clear Cell Sarcoma

Microsatellite Instability Analysis

KRAS Mutation

BRAF V600E Mutation

KIT Mutation in GIST

KIT Mutation in Melanoma

HER2 FISH, Breast cancer

UroVysion FISH, Bladder cancer

Genetics/Pharacogenomics

Cystic Fibrosis Carrier Screening

Apolipoprotein E Genotyping

Hereditary Hemochromatosis Mutation Detection

Factor V Leiden Mutation Detection

Methylenetetrahydrofolate Reductase C677T Mutation

Prothrombin 20210 Mutation

UGT1A1 Promoter Genotyping

Warfarin Sensitivity Analysis

Identity Testing

Bone Marrow Transplant Engraftment Analysis


My Day to Day Activities Medicine

  • Clinical

    • • Direct the development, validation, and implementation of new molecular tests

    • • Technical oversight and trouble shooting of existing tests

    • • Maintain quality control and quality assurance standards

    • • Daily review of test data

  • Teaching

    • • MGP fellows and block E residents

  • Research/Academic

    • • Novel molecular diagnostic tests and technologies

    • • Collaborations with AP and HP faculty


New Tests Since July 2007 Medicine

Hematologic Malignancies

Quantitative BCR/ABL

BCR/ABL1 Kinase Mutation Analysis

FLT3 Gene Mutation

NPM1 Mutation

CEBPA Mutation

KIT D816V Mutation

t(15;17) PML/RARA Translocation

t(14;18) IGH/BCL2 Translocation

B Cell (IGH) Gene Rearrangement

T Cell Gamma (TRG) Gene Rearrangement

JAK2 V617F Mutation Detection

JAK2 Exon 12 Mutations (March 2010)

Solid Tumor

PAX/FOXO1 Translocation, Alveolar Rhabdomyosarcoma

EWSR1/WT1 Translocation, DSRT

EWS/FLI1, EWS/ERG Translocations, Ewing Sarcoma

SYT/SSX Translocation, Synovial Sarcoma

EWS/ATF1 Translocation, Clear Cell Sarcoma

Microsatellite Instability Analysis

KRAS Mutation

BRAF V600E Mutation

KIT Mutation in GIST

KIT Mutation in Melanoma

HER2 FISH, Breast cancer

UroVysion FISH, Bladder cancer

Genetics/Pharacogenomics

Cystic Fibrosis Carrier Screening

Apolipoprotein E Genotyping

Hereditary Hemochromatosis Mutation Detection

Factor V Leiden Mutation Detection

Methylenetetrahydrofolate Reductase C677T Mutation

Prothrombin 20210 Mutation

UGT1A1 Promoter Genotyping

Warfarin Sensitivity Analysis

Identity Testing

Bone Marrow Transplant Engraftment Analysis


Molecular Diagnostics - Oncology Medicine

Diagnosis

Prognosis

Predict response to therapy

Monitor residual disease


Diagnosis – Ewing Sarcoma Medicine

Reverse

transcription

cDNA

EWSR1

primer

FLI1

primer

PCR

Extract

RNA

EWSR1/FLI1

~ 1 billion copies of target cDNA


PCR products Medicine

Detection

Capillary electrophoresis

EWSR1/FLI1 (Type 1)

GAPDH control


Molecular Diagnostics - Oncology Medicine

Diagnosis

Prognosis

Predict response to therapy

Monitor residual disease


Prognosis - Normal Karyotype AML Medicine

CEBPAmut

NPM1mutFLT3-ITDneg

Other genotypes

Schlenk RF et al. NEJM 358(18):1909, 2008


Prognostic Molecular Testing in AML – The UM Experience Medicine

Tests per Month

2004

2005

2006

2007

2008

2009


Molecular Diagnostics - Oncology Medicine

Diagnosis

Prognosis

Predict response to therapy

Monitor residual disease


Predict Response to Therapy: KIT Mutations in Melanoma Medicine

(4 wk)

Hodi FS et al., 2008 J Clin Oncol 26(12):2046


Molecular Diagnostics - Oncology Medicine

Diagnosis

Prognosis

Predict response to therapy

Monitor residual disease


Monitoring Residual Disease – UroVysion FISH Medicine

Malignant Urothelial Cell

Normal Urothelial Cell

CEP 3

LSI 9p21

CEP 7

CEP 17


Monitoring Residual Disease – UroVysion FISH Medicine

Case 4

History of CIS (bladder), Post Resection

Recurrence of CIS, BCG therapy, Monitoring

Cystoscopy - Negative

FISH - Positive


Thanks! Medicine


ad