Test Catalog

Test Id : IDHQ

Order This Test

IDH1 (R132) and IDH2 (R140 and R172) Quantitative Detection, Droplet Digital PCR, Varies

Download
Overview

Test Catalog

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

Detecting IDH1 R132 and IDH2 R140 and R172 mutations in acute myeloid leukemia patients at the time of diagnosis to guide targeted therapy

 

Monitoring minimal residual disease during the clinical and therapeutic course

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

A highly sensitive quantitative assay for the detection of 6 IDH1 R132 mutations (R132H, R132S, R132C, R132G, R132P, and R132L) and 10 IDH2 mutations R140 (R140Q, R140L, R140G, R140W) and R172 (R172K, R172M, R172G, R172S[G>C], R172S[G>T], R172W).

Highlights

The test can be used at the time of acute myeloid leukemia diagnosis to guide targeted therapy, as well as minimal residual disease monitoring markers during the clinical and therapeutic course of these patients.

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

Droplet Digital Polymerase Chain Reaction (ddPCR)

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

IDH1 and IDH2, Quant, ddPCR, V

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

Isocitrate dehydrogenase 1

Isocitrate dehydrogenase 2

IDHQ

IDH1

IDH2

AML

Ivosidenib

Azacitidine

Specimen Type
Describes the specimen type validated for testing

Varies

Shipping Instructions

1. Refrigerated specimens must arrive within 14 days of collection, and ambient specimens must arrive within 7 days of collection.

2. Collect and package specimen as close to shipping time as possible.

Necessary Information

The following information is required:

1. Pertinent clinical history

2. Date of collection

3. Specimen source (blood or bone marrow)

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
MP063 Specimen Type Peripheral blood
Bone marrow
Extracted DNA from peripheral blood
Extracted DNA from bone marrow

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: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD-B) or green top (heparin)

Specimen Volume: 4mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

3. Label specimen as blood.

Specimen Stability: Refrigerated 14 days/ Ambient 7 days

 

Specimen Type: Bone marrow aspirate

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD-B) or green top (heparin)

Specimen Volume: 2mL

Collection Instructions:

1. Invert several times to mix bone marrow.

2. Send bone marrow specimen in original tube. Do not aliquot.

3. Label specimen as bone marrow.

Specimen Stability: Refrigerated 14 days/ Ambient 7 days

 

Specimen Type: Extracted DNA from blood or bone marrow

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

Specimen Volume: Entire specimen

Collection Instructions:

1. Label specimen as extracted DNA and source of specimen

2. Indicate volume and concentration of DNA on label. The required volume of DNA is at least 50 mcL at a concentration of 50 ng/mcL

Specimen Stability: Frozen (preferred)/Refrigerated

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

Forms

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

Whole blood: 4mL

Bone marrow: 2mL

Extracted DNA: 50 mcL at 50 ng/mcL

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

Gross hemolysis Reject
Moderately to severely clotted Reject

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 Refrigerated (preferred) 14 days
Ambient 7 days

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

Detecting IDH1 R132 and IDH2 R140 and R172 mutations in acute myeloid leukemia patients at the time of diagnosis to guide targeted therapy

 

Monitoring minimal residual disease during the clinical and therapeutic course

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

A highly sensitive quantitative assay for the detection of 6 IDH1 R132 mutations (R132H, R132S, R132C, R132G, R132P, and R132L) and 10 IDH2 mutations R140 (R140Q, R140L, R140G, R140W) and R172 (R172K, R172M, R172G, R172S[G>C], R172S[G>T], R172W).

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

Isocitrate dehydrogenase 1 (IDH1) is a cytosolic/peroxisomal enzyme involved in citric acid cycle and other cellular metabolic processes. It catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (a-KG), generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) from NADP(+). Isocitrate dehydrogenase 2 (IDH2) is a mitochondrial NADP(+)-dependent enzyme that catalyzes the oxidative decarboxylation of isocitrate to a- KG, generating NADPH from NADP(+). Mutations in codon R132 of IDH1 or R140 or R172 in IDH2 confer an abnormal enzyme activity that converts a-KG to D-2- hydroxyglutarate (2-HG) resulting in elevation of 2-HG and a hypermethylation state, associated in myeloid neoplasms including acute myeloid leukemia (AML). IDH1 and IDH2 point mutations are seen in approximately 5% to 33% de novo acute myeloid leukemia (AML) and 7% to 25% secondary AML.

 

The US Food and Drug Administration (FDA) has approved ivosidenib (AG-120) for the treatment of newly-diagnosed IDH1-mutated AML (patients 75 years of age and older or who have comorbidities that preclude the use of intensive induction chemotherapy) and relapsed/refractory AML in adult patients.(1) The FDA has also approved enasidenib (AG-221) for the treatment of IDH2-mutated relapsed/refractory AML.(2)

 

IDH1 and IDH2 have also been shown to be suitable minimal residual disease markers for AML post-therapy.

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

The assay is reported as positive or negative. In positive cases, the mutation and its variant allele fraction (VAF) are reported.

 

VAF%= (mutant copy number)/(mutant copy number + wild-type number)

 

The precision of this quantitative assay is excellent but interassay variability may occur such that result changes should not be considered significant if 2 single measurements differ by less than 0.5 log (3.16-folds).

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

Other IDH1 or IDH2 variants outside the 16 assay targets are not detected by this assay.

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

1. US Food and Drug Administration (FDA): Table of Pharmacogenomic Biomarkers in Drug Labeling. FDA; Updated March 29, 2022, Accessed August 3, 2022. Available at www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling

2. US Food and Drug Administration (FDA): FDA granted regular approval to enasidenib for the treatment of relapsed or refractory AML. FDA; August 1, 2017. Accessed August 10, 2022. Available at www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-regular-approval-enasidenib-treatment-relapsed-or-refractory-aml

3. Yang H, Ye D, Guan KL, Xiong Y: IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res. 2012 Oct;18(20): 5562-5571

4. Dohner H, Weisdorf DJ, Bloomfield CD: Acute myeloid leukemia. N Engl J Med. 2015 Sept;373(12):1136-1152

5. McKenney AS, Levine RL: Isocitrate dehydrogenase mutations in leukemia. J Clin Invest.2013 Sep;123(9):3672-3677

6. Pollyea DA: New drugs for acute myeloid leukemia inspired by genomics and when to use them. Hematology Am Soc Hematol Educ Program. 2018 Nov;2018(1):45-50

7. Stein EM, DiNardo CD, Pollyea DA, Fathi AT, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia Blood. 2017 Aug 10;130(6):722-731.

8. DiNardo CD, Stein EM, de Botton S, et al: Durable remissions with Ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018 Jun;378(25):2386-2398

9. Ok CY, Loghavi S, Sui D, et al: Persistent IDH1/2 mutations in remission can predict relapse in patients with acute myeloid leukemia. Haematologica 2019;104(2):305-311

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

This test will be performed on Bio-Rad QX200 digital polymerase chain reaction (PCR) system. Mutation-specific droplet digital PCR probes were designed using Thermo Fisher Scientific MGB (minorgroove binder) Taqman technology. The PCR reactions for each patient are placed into an 8-tube cartridge along with droplet generation oil. The cartridge is loaded onto the droplet generator instrument to partition each reaction into 20,000 nanoliter-sized droplets.

 

Droplets are transferred to a plate for PCR amplification. Targets are amplified by end-point PCR in each droplet. The QX200 automated droplet reader counts every acceptable droplet and measures fluorescence emissions from each droplet using two different fluorescence channels (FAM and VIC). QuantaSoft software measures the number of negative and positive droplets for each fluorophore in each sample. Poisson statistics are used to determine the concentration of mutant and wild type copies in the sample.(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 through Saturday

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.

4 to 8 days

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

Blood/bone marrow: 2 weeks; Extracted 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 account representative. 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. It 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

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
IDHQ IDH1 and IDH2, Quant, ddPCR, V 95772-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
MP063 Specimen Type 31208-2
618389 Interpretation 69047-9
618390 Signing Pathologist 18771-6

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 | PHP Pdf | CMS 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