Test Catalog

Test Id : NGAMT

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Next-Generation Sequencing Acute Myeloid Leukemia, Therapeutic Gene Mutation Panel (FLT3, IDH1, IDH2, TP53), Varies

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation of acute myeloid leukemia (AML) using a focused 4-gene panel at the time of diagnosis, or possibly relapsed or refractory disease, to help determine optimal (eg, targeted) therapeutic approaches

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes next-generation sequencing to evaluate for the following 4 genes: FLT3, IDH1, IDH2, and TP53.

Highlights

Next-generation sequencing detection of somatic gene mutations, including type, pattern, and distribution, has diagnostic, prognostic, and potential therapeutic implications for patients with hematologic cancers, such as acute myeloid leukemia (AML).

 

This test identifies targets for more accurate therapeutic management of AML.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Somatic Mutation Detection by Next-Generation Sequencing (NGS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

AML 4 Gene Panel, Therapeutic

Aliases
Lists additional common names for a test, as an aid in searching

FLT3

IDH1

IDH2

Next gen sequencing of leukemia (AML)

Next Gen Sequencing Test

NGS cancer panel, hematologic

NGS hematologic malignancies

Somatic mutation detection by next generation sequencing (NGS), hematologic

TP53

Enasidenib therapy

Midostaurin therapy

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

This test  is a subset of the NGSHM / OncoHeme Next-Generation Sequencing for Myeloid Neoplasms test and focuses more specifically on the gene mutations that are most utilized for therapeutic management of acute myeloid leukemias (AML). If a wider gene mutation analysis is desired, or the indication is for a myeloid malignancy other than AML, then NGSHM / OncoHeme Next-Generation Sequencing (NGS), Hematologic Neoplasms should be considered.

Shipping Instructions

Peripheral blood and bone marrow specimens must arrive within 14 days of collection.

Necessary Information

The following information is required:

1. Clinical diagnosis

2. Pertinent clinical history, including disease phase (diagnostic, remission, relapse/refractory) and therapy status (especially if patient has received a hematopoietic stem cell transplant).

3. Clinical or morphologic suspicion

4. Date of collection

5. Specimen source

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Submit only 1 of the following specimens:

 

Specimen Type: Bone marrow aspirate (preferred)

Container/Tube:

Preferred: EDTA (lavender top) or ACD (yellow top)

Acceptable: Heparin (green top)

Specimen Volume: 2 mL

Collection Instructions:

1. Invert several times to mix bone marrow.

2. Send specimen in original tube.

3. Label specimen as bone marrow.

Specimen Stability: Ambient (preferred)/Refrigerate

 

Specimen Type: Peripheral blood

Container/Tube:

Preferred: EDTA (lavender top) or ACD (yellow top)

Acceptable: Heparin (green top)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

3. Label specimen as blood.

Specimen Stability: Ambient (preferred)/Refrigerate

 

Specimen Type: Extracted DNA from blood or bone marrow

Container/Tube: 1.5- to 2-mL tube with indication of volume and concentration of the DNA

Specimen Volume: 100 uL at 20 ng/uL concentration

Collection Instructions: Label specimen as extracted DNA and source of specimen

Specimen Stability: Frozen (preferred)/Refrigerate/Ambient

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. Hematopathology Patient Information (T676) in Special Instructions

2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood, Bone Marrow: 1 mL

Extracted DNA: 100 mcL at 20 ng/mcL concentration

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK
Other Bone marrow biopsies Slides Paraffin shavings or frozen tissues and paraffin-embedded tissues Paraffin-embedded bone marrow aspirates Moderately to severely clotted

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred) 14 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluation of acute myeloid leukemia (AML) using a focused 4-gene panel at the time of diagnosis, or possibly relapsed or refractory disease, to help determine optimal (eg, targeted) therapeutic approaches

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes next-generation sequencing to evaluate for the following 4 genes: FLT3, IDH1, IDH2, and TP53.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Next-generation sequencing (NGS) is a comprehensive molecular diagnostic methodology that can interrogate multiple regions of genomic tumor DNA in a single assay. Many hematologic neoplasms, including acute myeloid leukemia (AML), are characterized by morphologic or phenotypic similarities, but can have characteristic somatic mutations in many genes. In addition, many cases of AML lack a clonal cytogenetic finding at diagnosis (normal karyotype) and can be better classified according to gene mutation profile. The presence and pattern of gene mutations in AML can provide critical prognostic information and may help in guiding therapeutic management decisions by physicians, particularly if targeted therapies are available.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

Mutations (gene alterations) identified, if present, using human reference genome build GRCh37 (hg19). An interpretive report will be provided.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is a targeted next-generation sequencing (NGS) (panel) assay that encompasses 4 genes with variable full exon, partial region (including select intronic or non-coding regions), or hot spot coverage (depending on specific locus). Therefore, this test will not detect other genetic abnormalities in genes or regions outside the specified target areas. The test detects single base substitutions (ie, point mutations), as well as small insertion or deletion type events, but it does not detect gene rearrangements (ie, translocations), gene fusions, copy number alterations, or large scale (segmental chromosome region) deletions and complex changes.

 

This assay does not distinguish between somatic and germline alterations in analyzed gene regions, particularly with variant allele frequencies (VAF) near 50% or 100%. If nucleotide alterations in genes associated with germline mutation syndromes are present and there is also a strong clinical suspicion or family history of malignant disease predisposition, additional genetic testing and appropriate counseling may be indicated. Mutation cells detected between 5% and 10% VAF may indicate low-level (ie, subclonal) tumor populations, although the clinical significance of these findings may not be clear. A low incidence of gene mutations associated with myeloid neoplasms can be detected in nonmalignant hematopoietic cells in individuals with advancing age (clonal hematopoiesis of indeterminate potential, CHIP) and these may not be clearly distinguishable from tumor-associated mutations. Some apparent mutations classified as variants of undetermined significance (VUS) may represent rare or low frequency polymorphisms.

 

Prior treatment for hematologic malignancy could affect the results obtained in this assay. In particular, prior allogeneic hematopoietic stem cell transplant (HSCT) may cause difficulties in resolving somatic or polymorphic alterations, or in assigning variant calls correctly to donor and recipient fractions, if pertinent clinical or laboratory information (eg, chimerism engraftment status) is not provided.

 

Correlation with clinical, histopathologic and additional laboratory findings is required for final interpretation of these results. The final interpretation of results for clinical management of the patient is the responsibility of the managing physician.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Patel JP, Levine RL: How do novel molecular genetic markers influence treatment decisions in acute myeloid leukemia? Hematology Am Soc Hematol Educ Program 2012;2012:28-34

2. Lindsley RC, Ebert BL: The biology and clinical impact of genetic lesions in myeloid malignancies. Blood 2013;23:3741-3748

3. Amatangelo MD, Quek L, Shih A, et al.: Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Blood 2017;130(6):732-741

4 Stone RM, Mandrekar SJ, Sanford BL, et al.: Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med 2017;377:454-464

5 Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017;130(6):722-731

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing is performed for the presence of a mutation in targeted regions of the following 4 genes: FLT3, IDH1, IDH2, and TP53. See Targeted Genes Interrogated by Next-Generation Sequencing, Acute Myeloid Leukemia, Therapeutic, 4-Gene Panel in Special Instructions for details regarding the targeted gene regions identified in this test. This is a laboratory-developed test using Research Use Only reagents. Extracted DNA from the clinical specimen is fragmented, adapter ligated, and a sequence library of fragments is prepared using a custom capture hybridization method. Individual patient samples are indexed ("bar-coded") for identification and the library is sequenced on an Illumina platform. Sequence data are processed through the Mayo Clinic Clinical Genome Sequencing Lab bioinformatics pipeline and a variant call file is generated for final analysis and reporting.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

14 to 21 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 year, DNA 3 Months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81120

81121

81245

81246

81352

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports