This document discusses genetic testing regulations in New York state and the addition of new oncology genetic tests at Montefiore Medical Center. Key points: 1. Genetic testing in New York is regulated by the state Department of Health and requires a clinical laboratory permit, director certification, successful proficiency testing, and reporting results only to authorized individuals like physicians. 2. Montefiore's molecular genetics and cytogenetics labs offer a variety of genetic tests and are looking to add new targeted sequencing panels for cancer therapies. 3. An advisory committee evaluates new tests based on analytical and clinical validity and utility, test volume, and CPT codes before adding them.

1. Targeted Sequencing for Known
Indicators of Specific Therapies
Harry Ostrer, M.D.
Director of Genetic and Genomic Testing

2. "Clinical laboratory" means a facility for the
microbiological, immunological, chemical,
hematological, biophysical, cytological,
pathological, genetic, or other examination of
materials derived from the human body, for the
purpose of obtaining information for the
diagnosis, prevention, or treatment of disease or
the assessment of a health condition or for
identification purposes.
NYS Public Health Law Article V Title V (s) 571 (1)
Genetic testing is regulated by the New York State
Department of Health

3. 10 NYCRR Section 58-1.1 Permit. (a) Permit means a clinical
laboratory … issued by the Commissioner of Health. No clinical
laboratory or blood bank shall be issued a permit in a category unless:
(1) its director or assistant director holds a certificate of
qualification in the category for which the permit is sought;
(2) the laboratory has been inspected and has corrected any
deficiencies found; and
(3) the laboratory has successfully participated in all required
proficiency examinations or remedial activities in the categories
sought.
(b) A clinical laboratory … shall perform only those tests that are
within the categories stated on its permit… Categories of tests
shall be designated according to the following procedures or
specialties:
(9) cytogenetics;
(15) other specific tests or procedures as designated by the
department. (i.e. molecular genetics, biochemical genetics,
paternity identity, forensic identity)
Genetic testing is regulated by the New York State
Department of Health

4. Public Health Law Article 5 Title V - 10 NYCRR 58.1
58-1.8 Results of tests to be reported only to physicians
or other authorized persons. No person shall report the
result of any test, examination or analysis of a
specimen submitted for evidence of human disease or
medical condition except to a physician, his agent, or
other person authorized by law to employ the results
thereof in the conduct of his practice or in the
fulfillment of his official duties. Reports shall not be
issued to the patients concerned except with the
written consent of the physician or other authorized
person, except that information concerning blood type
and Rh factor may be provided in writing to the
individual whose blood was tested without the consent
of the individual's physician.
Authorized Person for Lab Reporting

5. Genetic Testing at Montefiore Medical Center
Molecular Genetics Lab
Directors
Carole Oddoux, Ph.D.
Rizwan Naeem, M.D.
Harry Ostrer, M.D.
Test menu
Molecular virology
Molecular oncology
Germline molecular genetics
(Sequencing, genotyping,
aCGH, qPCR, MLPA)
Cytogenetics Lab
Directors
Linda Cannizzaro, Ph.D.
K.H. Ramesh, Ph.D.
Test menu
Germline cytogenetics
Cancer cytogenetics
(Karyotype and FISH)

6. Oncology Genetic Testing at Montefiore Medical Center
qPCR – bcr-abl diagnosis and residual disease/relapse
B&T cell clonality
FISH amplification (HER2)
translocations (t8:14)
Microsatellite instability (HNPCC germline risk)
Sequencing breast, ovarian and colon germline risk
actionable mutations for therapy

7. Addition of New Oncology Genetic Tests
Advisory committee
James Pullman, M.D., Ph.D.
Jerome Graber, M.D.
Christine McMahon, M.D.
Harry Ostrer, M.D.
Amit Verma , M.D.
Kathleen Whitney, M.D.
Criteria
Analytical validity
Clinical validity
Clinical utility
Test volume
CPT codes

8. ALK Non-squamous cell lung cancer
BRAF Colon cancer, melanoma
CDKN2A Melanoma
EGFR Non-squamous cell lung cancer
EZH2 MDS
FLT3 AML
JAK2
Myeloprofilerative neoplasms
(replacement test)
KIT Gastrointestinal stromal tumros
KRAS
Non-squamous cell lung cancer,
colon cancer
IDH1 MDS
IDH2 MDS
NPM1 AML
PDGFRA Gastrointestinal stromal tumros
TP53 MDS
Ion Torrent HotSpot Panel v2
50 gene
panel

9. Challenges with targeted sequencing for
known indicators of specific therapies
Variant calling SNV, indels – OK
CNVs, structural – challenging
Multiclonality ≥10%
Interpretation Manual curation
literature review
Rapidly changing environment
Germline risk  genetic counseling and consent

10. New York State Civil Rights Law Section 79L
Confidentiality of Records of Genetic Tests
(a) "genetic test" shall mean any laboratory test of human DNA,
chromosomes, genes, or gene products to diagnose the
presence of a genetic variation linked to a predisposition to a
genetic disease
(b) "genetic predisposition" shall mean the presence of a variation
in the composition of the genes of an individual… which is
determined to be associated with an increased statistical risk
of being expressed as either a physical or mental disease.
2. (a) No person shall perform a genetic test on a biological sample
taken from an individual without the prior written informed
consent of such individual
(c) A general waiver, wherein consent is secured for genetic testing
without compliance with paragraph (b) of this subdivision,
shall not constitute informed consent.

11. New York State Civil Rights Law Section 79L
Confidentiality of Records of Genetic Tests
Written informed consent to a genetic test shall consist of
written authorization that is dated and signed and
includes at least the following:
(1) a general description of the test;
(2) a statement of the purpose of the test;
(3) a statement indicating that the individual may wish to
obtain professional genetic counseling prior to
signing the informed consent.
(4) a statement that a positive test result is an indication
that the individual may be predisposed to or have the
specific disease or condition tested for and may wish
to consider further independent testing, consult their
physician or pursue genetic counseling;

12. ACMG Recommendations for Reporting of Incidental
Findings in Clinical Exome and Genome Sequencing
“We recommend that laboratories performing clinical sequencing
seek and report mutations of the specified classes or types in
the genes listed here. This evaluation and reporting should be
performed for all clinical germline (constitutional) exome and
genome sequencing, including the normal of tumor normal
subtractive analyses in all subjects, irrespective of age, but
excluding fetal samples. We recognize that there are
insufficient data on clinical utility to fully support these
recommendations and we encourage the creation of an
ongoing process for updating these recommendations at least
annually as further data are collected.”
List includes hereditary cancers, connective tissue disorders
(EDS, Marfan), cardiomyopathies, heritable arrythmias,
malignant hyperthermia.
Genet Med. 2013;15:565-74.

13. How to get my new idea into practice?
Meet with Jim Pullman, Carole Oddoux and me
Present evidence for clinical validity/utility
Montefiore/other market