Bi-directional sequencing to detect nonsense, frameshift, and other mutations encoding the C-terminus of CXCR4. Analyzed range includes detection of the C1013G mutation and spans amino acids L301 to S352. Testing is available separately or in combination with three other contributory genes in the BTK Inhibitor Primary Susceptibility Panel. Testing is approved for specimens from the state of New York.
CXCR4 activates AKT1/MAPK pathways in B-lineage cells and facilitates cell migration in Waldenstrom macroglobulinemia (WM). Mutations are detected in nearly 30% of WM cases, and are associated with primary resistance and initial lack of response to BTK, PI3K, and mTOR inhibitors. The majority of these cases with CXCR4 mutations have concurrent MYD88 L265P mutations. The common C1013G mutation in CXCR4 and other somatic frameshift and nonsense mutations detected by this test are the same as or similar to the germline mutations associated with WHIM syndrome. Therapeutic antagonists to CXCR4 are in clinical trials.
- Peripheral blood: 5 mL in EDTA tube.
- Bone marrow: 2 mL in EDTA tube.
- FFPE tissue: Paraffin block is preferred. Alternatively, send 1 H&E slide plus 5-10 unstained slides cut at 5 or more microns. Please use positively-charged slides and 10% NBF fixative. Do not use zinc fixatives.
Use cold pack for transport. Make sure cold pack is not in direct contact with specimen.