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Alternative Name
STAT3 Gene Sequencing
Methodology
Molecular
Test Description

STAT3 mutation analysis is performed by next-generation sequencing of all coding exons of the STAT3 gene.

Clinical Significance

The STAT3 gene encodes a signaling protein regulating transcription of a wide range of genes, including those signaling the maturation of T cells and B cells. Constitutive STAT3 activation, as a result of upregulation or mutation, is seen in a variety of solid and hematopoietic cancers. STAT3 mutations, most often Y640F, D661V/Y/H/I, and N647I, have been described in 30-40% of T-cell large granular lymphocytic (T-LGL) leukemia, 30% of chronic natural killer lymphoproliferative disorders (CLPD-NK), and more rarely in aplastic anemia, MDS, and DLBCL. Identifying STAT3 mutations can help to differentiate LGL from reactive processes. T-LGL patients with STAT3 mutations tend to present with neutropenia and have a better prognosis than T-LGL patients without this mutation.  The JAK3 inhibitor, tofacitinib, has been shown to improve neutropenia in T-LGL patients, while T-LGL patients with a STAT3 Y640F mutation have been shown to be sensitive to methotrexate treatment.

Specimen Requirements
  • 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.
Storage and Transportation

Use cold pack for transport, making sure cold pack is not in direct contact with specimen.

CPT Code(s)*
81405
New York Approved
No
Level of Service
Global
Turnaround Time

14 days

References
  1. Wang Y, Shen Y, Wang S, Shen Q, Zhou X. The role of STAT3 in leading the crosstalk between human cancers and the immune system. Cancer Lett. 2018;415:117-128.
  2. Shahmarvand N, Nagy A, Shahryari J, Ohgami RS. Mutations in the signal transducer and activator of transcription family of genes in cancer. Cancer Sci. 2018;109(4):926-933.
  3. Teramo A, Barilà G, Calabretto G, et al. STAT3 mutation impacts biological and clinical features of T-LGL leukemia. Oncotarget. 2017;8(37):61876.
  4. Lamy T, Moignet A, Loughran TP. LGL leukemia: from pathogenesis to treatment. Blood. 2017;129(9):1082-1094.
  5. Moignet A, Lamy T. Latest advances in the diagnosis and treatment of large granular lymphocytic leukemia. American Society of Clinical Oncology Educational Book. 2018;38:616-625.

*The CPT codes provided with our test descriptions are based on AMA guidelines and are for informational purposes only. Correct CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.