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An Introduction to Use, Application, Technology and Coding

Molecular and Genetic Clinical Diagnostics . An Introduction to Use, Application, Technology and Coding. February 16, 2011. Results For Life: The Value of Laboratory Medicine. Message Laboratory medicine central to medical decisions

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An Introduction to Use, Application, Technology and Coding

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

  3. ACLA Members and Associate Members

  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

  5. Because we know vastly more about disease…

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

  7. Presented byVictoria Pratt, Ph.D., FACMG The Basics of Genetic Testing

  8. One of the most fundamental “basics” • 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

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

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

  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

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

  13. Human Chromosomes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y

  14. Gene Mutations Mismatch Deletion Deletion Insertion

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

  16. Different Genes, Different Functions Bone Cell Pancreas Cell Brain Cell

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

  18. Continuum of Diagnostic Lab Testing

  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

  20. New Assay/Biomarker Progression Retrospective clinical trials Prospective clinical trials Clinical Research Test Translation Clinical Validity Clinical Utility Biomarker associated with disease Lab test developed -Analyticalvalidation Test canpredict clinical outcomes Benefits patients

  21. Presented bySherri J Bale, Ph.D., FACMGVictoria Pratt, Ph.D., FACMG The Use and Value of Genetic Tests for Patients

  22. Genetic Tests for Constitutional Mutations • Cytogenetic Tests • Molecular Tests

  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

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

  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 Patient with Tetralogy of Fallot, Suspected 22q11 Deletion

  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.

  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.

  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

  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

  30. Personalized Medicine, Pharmacogenetics Getting the right dose, to the right patient, at the right time

  31. Chronic Myelogenous Leukemia

  32. Clopidogrel (Plavix®)

  33. Presented byVictoria Pratt, Ph.D., FACMG Emerging Technologies and Testing

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

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

  36. MicroRNAs (miRNA) • Single-stranded RNA molecules • 21-23 nt • Transcribed from non-coding DNA • Regulate gene expression • Cancer • May enable classification of cancers (CUP = cancer of unknown primary) • Determine therapy

  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

  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

  39. Genetic tests find mutations, not disease Chances of Developing Breast Cancer by Age 65 8 7 6 5 4 3 2 With BRCA 1 Gene Without BRCA 1 Gene Normal BRCA1 1 0 Altered BRCA1

  40. Presented byKaye Jones, MLS(ASCP), CPC Laboratory Procedures and Coding

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

  42. Molecular Codes • CPT codes 83890-83914 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: 83898 Amplification x3 83896 Nucleic acid probe, each x25

  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

  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 eachin order to interpret the assay).

  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

  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. • 88230 Tissue culture • 88262 Karyotyping • 88291 Interpretation and report with a picture of the actual chromosomes

  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

  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

  49. Molecular Diagnostics and Cytogenetics • Array CPTs 88384-88386 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

  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

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