• Test Code:
  • Department:
  • Test Synonyms:
    BTKBTK exon 14ibrutinib resistance mutation
  • CPT Code(s):

The mutation of p.C481S has been characterized as a known contributor to the resistance of the drug ibrutinib in patients being treated for CLL.


The interrogation of the C481 codon is performed in the following process:

  1. DNA extraction and purification
  2. PCR amplification of BTK exon 14
  3. Screening for the mutation by bidirectional sequencing

Specimen Requirements:

Preferred specimens:

  • Blood or Bone Marrow: 5-10 mL purple (EDTA) or yellow (ADC) tube (unspun)

Acceptable specimens:

  • Paraffin block or 10 unstained sections of tumor or bone marrow
  • DNA: 150ng at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information.

Test Performed (Days):


Turn Around Time:

7-10 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services at (855) 535-1522 for shipping kits and instructions.


  1. Woyach J et al. Resistance mechanisms for the Bruton’s tyrosine kinase inhibitor Ibrutinib. N Engl J Med 2014;370:2286-94.
  2. Chiron et al. Cell cycle reprogamming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov; 4(9); 00-00.2014 AACR.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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