Test ID: JAKXB
JAK2 Exon 12 and Other Non-V617F Mutation Detection, Blood
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Aiding in the distinction between a reactive cytosis and a myeloproliferative neoplasm, particularly when a diagnosis of polycythemia is being entertained
This is a second-order test that should be used when the test for the JAK2B/88715 JAK2 V617F Mutation Detection, Blood test is negative.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
See Myeloproliferative Neoplasm: A Diagnostic Approach to Peripheral Blood Evaluation in Special Instructions
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Mutation Detection in cDNA Using Sanger Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
JAK2 Exon 13
JAK2 Exon 14
JAK2 Exon 15
Janus Kinase 2 Gene
Janus Kinase 2 Gene Sequencing
Tyrosine Kinase Gene Sequencing
Tyrosine Kinase Mutuation
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Specimen must arrive within 72 hours of draw.
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: ACD
Specimen Volume: 4 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Additional Information: Date of draw is required.
Forms:
1. Hematopathology Patient Information Sheet (Supply T676) in Special Instructions
2. If not ordering electronically, submit a Hematopathology/Molecular Oncology Request Form (Supply T241) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood | Ambient (preferred) | 72 hours |
| Refrigerated | 72 hours |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
DNA sequence mutations in the Janus kinase 2 gene (JAK2) are found in the hematopoietic cells of several myeloproliferative neoplasms (MPNs), most frequently polycythemia vera (close to 100%), essential thrombocythemia (approximately 50%), and primary myelofibrosis (approximately 50%). Mutations in JAK2 have been reported at much lower frequency in other MPNs, chronic myelomonocytic leukemia and mixed MPN/myelodysplastic syndromes, but essentially never in chronic myelogenous leukemia (CML), reactive cytoses, or normal patients. Mutations are believed to cause constitutive activation of the JAK2 protein, which is an intracellular tyrosine kinase important for signal transduction in many hematopoietic cells. Since it is often difficult to distinguish reactive conditions from the non-CML MPNs, identification of a JAK2 mutation has diagnostic value. Potential prognostic significance of JAK2 mutation detection in chronic myeloid disorders has yet to be clearly established.
The vast majority of JAK2 mutations occur as base pair 1849 in the gene, resulting in a JAK2 V617F protein change. In all cases being evaluated for JAK2 mutation status, the initial test that should be ordered is JAK2B/88715 JAK2 V617F Mutation Detection, Blood, a sensitive assay for detection of the mutation. However, if no JAK2 V617F mutation is found, further evaluation of JAK2 may be clinically indicated. Over 50 different mutations have now been reported within exons 12 through 15 of JAK2 and essentially all of the non-V617F mutations have been identified in polycythemia vera. These mutations include point mutations and small insertions or deletions. Several of the exon 12 mutations have been shown to have biologic effects similar to those caused by the V617F mutation such that it is currently assumed other nonpolymorphic mutations have similar clinical effects. However, research in this area is ongoing.
This assay for non-V617F/alternative JAK2 mutations is designed to obtain the sequence for JAK2 exons 12 through the first 90% of exon 15, which spans the region containing all mutations reported to date.
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 results will be reported as 1 of 2 states:
1. Negative for JAK2 mutation
2. Positive for JAK2 mutation
If the result is positive, a description of the mutation at the nucleotide level and the altered protein sequence is reported.
Positive mutation status is highly suggestive of a myeloproliferative neoplasm, but must be correlated with clinical and other laboratory features for a definitive diagnosis. Negative mutation status does not exclude the presence of a myeloproliferative or other neoplasm.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A positive result is not specific for a particular diagnosis and clinico-pathologic correlation is necessary in all cases. A negative result does not exclude the presence of a myeloproliferative or other neoplasm.
The sensitivity of this assay is much less than that of JAK2B/88715 JAK2 V617F Mutation Detection, Blood. This is because the sequencing technique is required to evaluate for many potential mutations. The sensitive JAK2B/88715 JAK2 V617F Mutation Detection, Blood should always be performed first, as the JAK2 mutation burden may be very low in some specimens. If JAK2B/88715 JAK2 V617F Mutation Detection, Blood is negative, then this assay JAKXB/89189 JAK2 Exon 12 and Other Non-V617F Mutation Detection, Blood should be performed for detection of non-V617F JAK2 mutations.
Supportive Data
Analytical sensitivity is approximately 20% meaning there must be about 20% of the mutated DNA in the sample for reliable detection.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Ma W, Kantarjian H, Zhang X, et al: Mutation profile of JAK2 transcripts in patients with chronic myeloid neoplasias. J Mol Diagn 2009;11:49-53
2. Kilpivaara O, Levine RL: JAK2 and MPL mutations in myelo-proliferative neoplasms: discovery and science. Leukemia 2008;22:1813-1817
3. Kravolics R: Genetic complexity of myeloproliferative neoplasms. Leukemia 2008;22:1841-1848
Method Description Describes how the test is performed and provides a method-specific reference
Total RNA is extracted from whole blood and cDNA synthesized from JAK2 mRNA. A fragment spanning exons 12 through 15 is then amplified using standard PCR and the sequence obtained using Sanger sequencing (BigDye terminator V1.1 cycle sequencing kit from Applied Bioscience) with analysis on an automated genetic analyzer.(Applied Biosystems 3130; unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81403-JAK2 (Janus kinase 2) (eg, myeloproliferative disorder), exon 12 sequence and exon 13 sequence, if performed
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 20194 | Final Diagnosis: | 34574-4 |
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