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1 An Introduction to Use, Application, Technology and Coding Molecular and Genetic Clinical Diagnostics February 16, 2011.

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Presentation on theme: "1 An Introduction to Use, Application, Technology and Coding Molecular and Genetic Clinical Diagnostics February 16, 2011."— Presentation transcript:

1 1 An Introduction to Use, Application, Technology and Coding Molecular and Genetic Clinical Diagnostics February 16, 2011

2 Results For Life: The Value of Laboratory Medicine Message – Laboratory medicine central to medical decisions – Laboratory medicine changes course of diagnosis, treatment, management Audience – Congress, media, thought leaders Tools – Briefings, OpEds, advertising 2

3 ACLA Members and Associate Members ACLA Member Sponsors Associate Members Aculabs Agendia Arista Laboratories ARUP Laboratories Aureon Laboratories Aurora Diagnostics Axial Biotech Berkeley Heartlab Biodesix BioReference Laboratories bioTheranostics CBLPath Clarient Cleveland Clinic Foundation CorePlus DaVita DCI Laboratory Genomic Health Genoptix GI Pathology, PLLC Joint Venture Hospital Labs Laboratory Corp of America Laboratory Partners Machaon Diagnostics Mayo Clinic MEDTOX Laboratories Meridian Laboratories Myriad Genetics NeoGenomics Laboratories NMS Labs PathNet Esoteric Lab Inst Pathology Associates Medical Laboratories Pathology PerkinElmer Genetics Precision Therapeutics Quest Diagnostics Incorporated RenaLab RedPath Integrated Pathology Satellite Laboratory Services Solstas Lab Partners Spectra Laboratories Tethys Bioscience TridentUSA Health Services Virco Lab XDx Abbott Molecular American Medical Technologists Aperio Cgate Health HillCo Health LipoScience McKesson Health Solutions-Adv Diagn. Mgt Roche Siemens Sysmex XIFIN 3

4 A revolution in science requires a revolution in thinking What disease is How to identify and treat disease When it is best to take action Which individuals are at risk The size of the population we treat The economics of utilization and health spending The ability to reduce adverse events, side effects, inappropriate use 4

5 Because we know vastly more about disease… 5 Diagnose more preciselyMore effective treatment Select specific treatment that best fits disease Avoid adverse drug reaction Improve utilization Predict risk before symptoms occur Earlier treatment Preventive action Manage more effectively Better timing Adjustments as disease changes

6 Today The basics of genetic testing The use and value of genetic testing – Personalized medicine – Pharmacogenomics – Emerging Technologies Laboratory procedures and coding 6 Presentation Speakers  Vicky Pratt, Ph.D., FACMG, Quest Diagnostics  Sherri Bale, Ph.D., FACMG, GeneDX  Kaye Jones, MLS (ASCP), CPC, LabCorp

7 7 Presented by Victoria Pratt, Ph.D., FACMG T HE B ASICS OF G ENETIC T ESTING

8 Diagnostic laboratory testing drives health decisions – 70% of healthcare decisions based on diagnostic data Diagnostic data yields essential information – Helps identify trends for public health – Enables physicians to care for individual patients – Facilitates new test development Continuum of diagnostic lab testing – From diagnosis to predictive and personalized medicine Diagnostic data increasingly… – … is providing actionable insights physicians can use to improve patient healthcare outcomes 8 One of the most fundamental “basics”

9 Nucleus DNA bases mRNA DNA Protein Ribosome Cell membrane Gene Chain of amino acids DNA » RNA » Protein 9

10 Chromosome Cytogenetics Protein Biochemical Genetics DNA Molecular Genetics Gene Tests: Three Common Methods 10 Mutation AbsentMutation Present

11 Types of Mutations Single nucleotide - traditional – Missense – Nonsense (creation of stop codon) – Splicing – Regulatory sequences (promoter, 3’ end) Deletions/Insertions – copy number variants (CNVs) – In frame – frameshift Expansions (triplet repeat disorders) Epigenetic (methylation) Translocations and inversions 11

12 Dominant Allele Quiet! I’ll speak for both of us! Damaged Allele Normal Allele Recessive Allele I’ll have to be in charge now! Alleles 12

13 X Y Human Chromosomes 13

14 Mismatch Insertion Deletion Gene Mutations 14

15 General Principles Hereditary disorders can affect multiple organs Penetrance can be influenced by modifiers: genes + environment Complexity of mutational spectrum varies 15

16 Pancreas CellBone CellBrain Cell Different Genes, Different Functions 16

17 Mutation 2 No Symptoms Mucus Production Gene Normal No Symptoms Mild Symptoms Severe Symptoms Mutation 1Mutation 3 Gene Changes in Cystic Fibrosis Gene inheritance is complex 17

18 Continuum of Diagnostic Lab Testing 18

19 Common genetic disorders Inherited (predictive or diagnostic) – Cystic fibrosis – Thrombophilia – Hereditary hemochromatosis – Fragile X syndrome Acquired (predictive or diagnostic) – Chronic myelogenous leukemia (CML) Pharmacogenetics (personalized) – Cytochrome P450s – HLA 19

20 New Assay/Biomarker Progression 20 C LINICAL R ESEARCH T EST T RANSLATION C LINICAL V ALIDITY C LINICAL U TILITY Biomarker associated with disease Lab test developed - Analytical validation Test can predict clinical outcomes Benefits patients Retrospective clinical trials Prospective clinical trials

21 21 Presented by Sherri J Bale, Ph.D., FACMG Victoria Pratt, Ph.D., FACMG T HE U SE AND V ALUE OF G ENETIC T ESTS FOR P ATIENTS

22 Genetic Tests for Constitutional Mutations Cytogenetic Tests Molecular Tests 22

23 Cytogenetic Test Standard karyotype, used to look for gross chromosomal anomalies in children with development delays, congenital anomalies, mental retardation FISH, used to look at 1 or 2 specific chromosomal regions suspected by the physician BAC arrays, used to look at many (100s) chromosomal regions at once, using FISH technology CGH array, used to look at MANY (50K-200K) regions at once, and identify specifically which genes are involved in the chromosomal anomaly 23

24 Child with Multiple Congenital Anomalies and/or Autism 24 Standard karyotypeCGH array - “molecular karyotype”

25 Patient with Tetralogy of Fallot, Suspected 22q11 Deletion 25 FISH test, 2 probes: – used in baby – found deletion – confirmed dx – Provided prognostic info to family. Parents tested by FISH: – Negative – Provided information re: risk in future children

26 Child with Multiple Anomalies and Autism; No Specific Syndrome Suspected Karyotype normal CGH array followed Karyotype. – Identified deletion involving end of one arm of chromosome 3 Parents tested by FISH and dad found to be balanced carrier of the deletion Prenatal diagnosis by quantitative PCR is now possible for the family. 26

27 Molecular Test – PCR, followed by sequencing, for identification of mutation Used to identify mutation in a patient with inherited disease Number of times PCR is done and how much sequencing is required depends on SIZE of gene, MANY UNITS. Once mutation is identified, testing of parents, sibs, other relatives for ONLY that mutation, is needed. ONE or ONLY a FEW UNITS. 27

28 Molecular diagnosis of Gorlin Syndrome 13 yo child presented to dentist with a jaw cyst – surgery performed but tooth was lost. Referred to geneticist. Geneticist suspected Gorlin Syndrome Molecular diagnosis involved PCR and sequencing, 26 “units” (large gene). Mutation identified. Prognosis now known: This individual would develop many skin cancers, more jaw cysts. Regular surveillance by dermatologist and dentist allowed early identification, less expensive treatment, and good clinical outcome: – Teeth were saved; Minimal damage to nose, ears, eyes 28

29 Use and Value of Genetic Tests Diagnosis – Enables physicians to properly care for patient Prognosis – Appropriate surveillance leading to early care and intervention Risk Information – Is it inherited? What is the recurrence risk in future pregnancies? Prenatal/Pre-symptomatic diagnosis – Allows informed decision making, preventive care 29

30 Personalized Medicine, Pharmacogenetics 30

31 Chronic Myelogenous Leukemia 31 SciencePatient Care Fusion of BCR/ABL genes FISH, Quantitative PCR to identify Treatable with Gleevac Better response rates, less toxicity Complete remission in many patients 5-year survival rate: 69% in 2001, 89% now Some patients become resistant to Gleevac Mutations in tyrosine kinase domains (DNA sequencing)

32 Clopidogrel (Plavix®) 32 SciencePatient Care To inhibit blood clots in coronary artery disease, peripheral artery disease, and cerebrovascular disease. Metabolized by cytochrome P450 2C19 to active form FDA: clopidogrel cannot be taken with Prilosec (omeprazole) and Nexium (esomeprazole) Inhibitors of 2C19 Prevention of vascular ischemic events in patients with symptomatic artherosclerosis Also used, along with aspirin, for preventing thrombosis after placement of intracoronary stent

33 33 Presented by Victoria Pratt, Ph.D., FACMG E MERGING T ECHNOLOGIES AND T ESTING

34 The genome is complex High throughput DNA sequencing microRNAs Copy Number Variants (CNVs) Epigenetics – methylation Proteomics – Up and down regulation – Disease-specific patterns 34

35 New high throughput DNA (NextGen) sequencing methods Reduced the cost Increased sequencing capacity 454 (Roche) Solexa (Illumina) SOLiD (ABI) 35

36 MicroRNAs (miRNA) Single-stranded RNA molecules – nt – Transcribed from non-coding DNA Regulate gene expression Cancer – May enable classification of cancers (CUP = cancer of unknown primary) – Determine therapy 36

37 Copy Number Variants (CNVs) (Variome) Large deletions or duplications of DNA – Usually cannot be detected by DNA sequencing – Newer technologies aCGH Impacts – Autism – Alzheimer disease – Parkinson disease – susceptibility to HIV-1 – some forms of color blindness 37

38 Epigenetics Changes in chromatin structure (how DNA is packaged) or alters gene activity without changing the DNA – DNA methylation – Modification of histones – Position effects Cancer and imprinting disorders 38

39 Chances of Developing Breast Cancer by Age 65 Normal BRCA1 Altered BRCA Genetic tests find mutations, not disease 39 With BRCA 1 Gene Without BRCA 1 Gene

40 40 Presented by Kaye Jones, MLS(ASCP), CPC L ABORATORY P ROCEDURES AND C ODING

41 Objective To improve your understanding of current molecular diagnostic CPT coding 41

42 Molecular Codes CPT codes represent steps performed during molecular diagnostic procedures CPT codes are assigned based on the different steps and the number of times each type of step is performed. Example: Amplification x Nucleic acid probe, each x25 42

43 Molecular Codes Different molecular methods may be used for the same analyte Those methods may vary among different laboratories. Therefore, different labs may code their tests differently 43

44 Molecular Codes No clear written guidelines for how to assign units of service Example: When a Cystic Fibrosis procedure for 23 mutations is performed by two different labs – One lab bills for 23 probes (1 per mutation). – The other lab bills for 46 probes (2 per mutation because you need a normal and a mutant probe for each in order to interpret the assay). 44

45 Molecular Codes All industry stakeholders recognize the issues surrounding the assignment and billing of molecular diagnostic procedures A number of organizations and entities are engaged in a collaborative process to review and address coding issues in an effort to increase transparency 45

46 Cytogenetics This is another area where CPT codes are assigned based on the procedural steps performed. Routine chromosome analysis typically requires three steps to complete the procedure. – Tissue culture – Karyotyping – Interpretation and report with a picture of the actual chromosomes 46

47 Cytogenetics Cytogenetic FISH is often necessary to diagnose constitutional defects Cytogenetic FISH may also be a stand alone order necessary to evaluate leukemias such as CML and MM Units of service are determined by the number of FISH probes and specific procedures needed to evaluate the cells 47

48 Molecular Diagnostics and Cytogenetics Think of newer CGH procedure as a combination of molecular diagnostic procedural steps needed to prepare the patient’s sample, and the cytogenetic CGH chip analysis There is much confusion within the industry regarding how to assign CPT codes to CGH procedures 48

49 Molecular Diagnostics and Cytogenetics Array CPTs are in the Surgical Pathology section of CPT. These codes are – global codes with Technical and Professional components, – only represent the work needed for the array chip and I&R – sample preparation is coded with molecular diagnostic codes – only appropriate for when a physician/pathologist performs the I&R 49

50 Molecular and Cytogenetic Codes In summary: – Molecular procedures are coded based on the procedural steps – Units of service are determined by the number of times each step is performed – Different procedures may exist for the same analyte, which makes the CPT coding different – Lack of standardized coding guidelines add to the complexities of how to assign CPTs 50

51 Thank you For more information, contact: David Mongillo, Vice President for Policy and Medical Affairs American Clinical Laboratory Association


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