Test Catalog

Test Id : CXCFX

MYD88 Reflex to CXCR4 Mutation Detection, Varies

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

The prognosis and clinical management of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia

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

Only orderable as a reflex. For more information see LPLFX / Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia, MYD88 L265P with Reflex to CXCR4, Varies.

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

CXCR4, Gene Mutation, Reflex

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

B-cell lymphoma

L265P

LPL/WM

Lymphoplasmacytic lymphoma

MYD88

CXCR4

Waldenstrom Macroglobulinemia

S338X

CXLPL

LPLFX

Specimen Type
Describes the specimen type validated for testing

Varies

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

Only orderable as a reflex. For more information see LPLFX / Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia, MYD88 L265P with Reflex to CXCR4, Varies.

 

Submit only 1 of the following specimens:

 

Specimen Type:  Blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD solution B)

Specimen Volume: 3 mL

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: Ambient (preferred)/Refrigerated

 

Specimen Type: Bone marrow

Container/Tube: Lavender top (EDTA) or yellow top (ACD solution B)

Specimen Volume: 2 mL

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: Ambient (preferred)/Refrigerated

 

Specimen Type: Extracted DNA

Container/Tube: 1.5- to 2-mL tube

Specimen Volume: Entire specimen

Collection Instructions:

1. Label specimen as extracted DNA and list specimen source.

2. Provide volume and concentration of the DNA.

Specimen Stability: Frozen (preferred)/Refrigerated/Ambient

 

Specimen Type: Paraffin-embedded tissue

Container/Tube: Paraffin block

Specimen Stability: Ambient

 

Specimen Type: Paraffin-embedded bone marrow aspirate clot

Container/Tube: Paraffin block

Specimen Stability: Ambient

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: 20 mcL with a concentration of at least 10 nanograms per mcL

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

Gross hemolysis OK
B5-fixed tissues
Bone marrow biopsies
Frozen tissue
Methanol acetic acid (MAA)-fixed pellets
Moderately to severely clotted
Paraffin shavings
Slides
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 Varies 10 days

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

The prognosis and clinical management of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia

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

Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) is a B-cell lymphoma characterized by an aberrant accumulation of malignant lymphoplasmacytic cells in the bone marrow, lymph nodes, and spleen. It is a B-cell neoplasm that can exhibit excess production of serum IgM symptoms related to hyper viscosity, tissue filtration, and autoimmune-related pathology. CXCR4 mutations are identified in approximately 30% to 40% of patients with LPL/WM and are almost always in association with MYD88 L265P, which is highly prevalent in this neoplasm. The status of CXCR4 mutations in the context of MYD88 L265P is clinically relevant as important determinants of clinical presentation, overall survival, and therapeutic response to ibrutinib: A MYD88-L265P/CXCR4-WHIM (C-terminus nonsense/frameshift mutations) molecular signature is associated with intermediate to high bone marrow disease burden and serum IgM levels, less adenopathy, and intermediate response to ibrutinib in previously treated patients. A MYD88-L265P/CXCR4-WT (wild type) molecular signature is associated with intermediate bone marrow disease burden and serum IgM levels, more adenopathy, and highest response to ibrutinib in previously treated patients. The MYD88-WT/CXCR4-WT molecular signature is associated with inferior overall survival, lower response to ibrutinib therapy in previously treated patients, and lower bone marrow disease burden in comparison to those harboring a MYD88-L265 mutation. This test is used to aid in the prognostication and therapeutic management of LPL/WM.

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.

Only orderable as a reflex. For more information see LPLFX / Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia, MYD88 L265P with Reflex to CXCR4, Varies.

 

An interpretive report will be provided

Interpretation
Provides information to assist in interpretation of the test results

Mutations detected or not detected.

 

An interpretive report will be issued under LPLFX / Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia, MYD88 L265P with Reflex to CXCR4, Varies.

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 assay for the C-terminus end of the CXCR4 gene only. It examines c.898-1059 of the CXCR4 gene (NCBI NM_003467.2 GRCh37) and does not detect variants outside this region. A 1% analytical sensitivity was established at 50-ng DNA input for the hotspot mutations c.1013C>G/A only, which uses bridged nucleic acids clamped Sanger sequencing, and DNA not meeting established criteria can lead to false-negative results. In the extremely rare event that a rare polymorphism or indel may occur at the Sanger sequencing primer binding sites, in cis, with c.1013C>G/A, data can yield a failed result. Routine Sanger sequencing is used to interrogate other mutations in the tested region with a 15% to 20% analytical sensitivity. The analytical sensitivity of the assay can be affected by a variety of factors, including biologic availability (ie, tumor burden), fixation of paraffin-embedded specimens, rare polymorphisms, or indels at the primer binding sites or nonspecific polymerase chain reaction interferences.

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

1. Hunter Z, Xu L, Yang G, et al: The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood. 2014 Mar 13;123(11):1637-1646. doi: 10.1182/blood-2013-09-525808

2. Landgren O, Tageja N: MYD88 and beyond: novel opportunities for diagnosis, prognosis and treatment in Waldenstrom's Macroglobulinemia. Leukemia. 2014 Sep;28(9):1799-1803. doi: 10.1038/leu.2014.88

3. Poulain S, Roumier C, Venet-Caillault A, et al: Genomic Landscape of CXCR4 Mutations in Waldenstrom Macroglobulinemia. Clin Cancer Res. 2016 Mar 15;22(6):1480-1488. doi: 10.1158/1078-0432.CCR-15-0646

4. Roccaro A, Sacco A, Jimenez C, et al: C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma. Blood. 2014 Jun 26;123(26):4120-4131. doi: 10.1182/blood-2014-03-564583

5. Schmidt J, Federmann B, Schindler N, et al: MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity. Br J Haematol. 2015 Jun;169(6):795-803. doi: 10.1111/bjh.13361

6. Treon SP, Cao Y, Xu L, Yang G, Liu X, Hunter ZR: Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia. Blood. 2014 May 1;123(18):2791-2796. doi: 10.1182/blood-2014-01-550905

7. Treon SP, Tripsas CK, Meid K, et al: Ibrutinib in previously treated Waldenstrom's macroglobulinemia. N Engl J Med. 2015 Apr 9;372(15):1430-1440. doi: 10.1056/NEJMoa1501548

8. Xu L, Hunter ZR, Tsakmaklis N, et al: Clonal architecture of CXCR4 WHIM-like mutations in Waldenstrom Macroglobulinaemia. Br J Haematol. 2016 Mar;172(5):735-744. doi: 10.1111/bjh.13897

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

The C-terminus end of CXCR4 (NM_003467.2, c.898-1059) is amplified from extracted genomic DNA by polymerase chain reaction, followed by Sanger sequencing and capillary electrophoresis analysis. Review of the sequence data is performed using a combination of automated calls and manual inspection.(Unpublished Mayo method)

 

The hotspot mutations c.1013C>G/A (p.S338X) are examined using bridged nucleic acids clamped Sanger sequencing with an analytic sensitivity of 1%. All other genetic mutations in the test region are examined by routine Sanger sequencing with an analytic sensitivity of 15% to 20%.(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 Friday

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.

7 days

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

DNA: 3 months; Blood, bone marrow: 2 weeks

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.

81479-Unlisted molecular pathology procedure

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