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What is the NAB2-STAT6 Gene Fusion in SFT?

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The NAB2-STAT6 gene fusion is a spontaneous genetic error that causes solitary fibrous tumors (SFT) to form. It is an acquired mutation, meaning it is not inherited. Testing positive for the STAT6 protein is the gold standard pathologists use to definitively confirm an SFT diagnosis.

Key Takeaways

  • • The NAB2-STAT6 gene fusion is the underlying genetic mutation responsible for solitary fibrous tumors.
  • • This fusion is a spontaneous, acquired mutation that occurs in a single cell and is not inherited.
  • • Testing positive for STAT6 nuclear expression is the gold standard for accurately diagnosing SFT.
  • • While there are no approved therapies that directly target this specific mutation, clinical trials are actively researching new options.

When you read a pathology report for a solitary fibrous tumor (SFT), you will almost certainly see terms like “NAB2-STAT6”, “IHC: STAT6+”, or “positive for STAT6 nuclear expression”.

The NAB2-STAT6 gene fusion is the underlying genetic change that causes solitary fibrous tumors to develop. Because this specific change is unique to SFT, testing for the STAT6 protein is the “gold standard” for confirming your diagnosis.

An Acquired Error, Not Inherited

When you see the word “genetic,” it is natural to worry that this is something you inherited from your parents or could pass on to your children. This is not the case.

The NAB2-STAT6 fusion is a somatic mutation, meaning it is a spontaneous error that happened by chance in a single cell during your lifetime [1][2]. It is not an inherited condition [3].

How the NAB2-STAT6 Fusion Happens

In every cell of your body, genes provide the instructions for how cells should grow, function, and behave. The NAB2 and STAT6 genes are normally located close to each other on chromosome 12 [3]. In a solitary fibrous tumor, a physical error occurs within the DNA of a single cell: a piece of the chromosome flips or folds back on itself [3][1].

This physical flip causes the NAB2 gene and the STAT6 gene to break and merge together, creating a new, abnormal gene known as a gene fusion [3][4].

Note: Because the genes can break and merge in slightly different places, your report might mention a specific “variant” (for example, “NAB2ex4-STAT6ex2”) [5]. This simply describes exactly where the two genes connected.

How This Mutation Drives Tumor Growth

To understand why this merged gene causes a tumor to form, it helps to know what the two original genes normally do:

  • NAB2 usually acts as an “off switch” (a repressor) that stops the cell from reading certain growth signals, preventing the cell from multiplying when it shouldn’t [6][7].
  • STAT6 usually acts as an “on switch” (an activator) that tells the cell to grow and multiply when needed [6].

When these two genes fuse together, the “on switch” part of STAT6 gets stuck to the control system of NAB2 [6][7]. The resulting abnormal protein completely loses its ability to turn off growth [6]. Instead, it acts as a permanent “on” signal, continuously telling the cell to divide, grow, and survive [6][7]. Over time, these constantly growing cells accumulate and form a tumor [8][9].

Why STAT6 Testing is the Gold Standard for Diagnosis

Solitary fibrous tumors look very similar to many other types of soft tissue sarcomas and benign tumors under a microscope [10][11]. In the past, this made SFT difficult to diagnose accurately.

However, researchers discovered that the abnormal NAB2-STAT6 fusion protein naturally travels to the nucleus (the control center) of the tumor cells [4][12]. Normal cells do not have STAT6 concentrated in their nuclei in this way.

Pathologists use a laboratory test called immunohistochemistry (IHC) to apply a special stain to your tumor biopsy tissue. If the tumor is an SFT, the stain will detect high levels of the STAT6 protein in the nuclei of the cells [13][14].

This nuclear STAT6 stain is considered the gold standard for diagnosis because it is:

  • Highly Sensitive: Almost all solitary fibrous tumors will test positive for STAT6 in the nucleus [13][15].
  • Highly Specific: Very few other types of tumors have this feature, allowing pathologists to definitively separate SFT from other mimics [16][17].

By confirming the presence of the STAT6 protein, your medical team can be highly confident in your SFT diagnosis [13][16]. In the rare event that the IHC stain is unclear, or if a tumor is suspected to be SFT but tests negative for STAT6, doctors can use specialized genetic sequencing to look directly for the fused DNA to confirm the diagnosis [3].

Is There a Targeted Therapy?

Because this mutation is the driver of the tumor, you might wonder if there is a medication specifically designed to target it. Currently, there are no FDA-approved drugs that specifically target or turn off the NAB2-STAT6 fusion [4][18].

The presence of the mutation is primarily used to confirm the diagnosis. If systemic treatment is needed, doctors typically use other types of medications, such as anti-angiogenic drugs that starve the tumor of blood flow [19][20]. However, researchers are actively studying new ways to target this gene fusion in clinical trials [18][21].

Frequently Asked Questions

Is the NAB2-STAT6 gene fusion inherited?
No, this genetic change is a somatic mutation, which means it happens spontaneously in a single cell during your lifetime. It is not inherited from your parents and you cannot pass it on to your children.
What does STAT6 positive mean on my SFT pathology report?
A STAT6 positive result means that the abnormal STAT6 protein was found concentrated inside the nucleus of your tumor cells. This specific finding is the gold standard test used by pathologists to confirm a solitary fibrous tumor diagnosis and distinguish it from other similar conditions.
Is there a targeted therapy for the NAB2-STAT6 mutation?
Currently, there are no FDA-approved drugs designed specifically to target or turn off the NAB2-STAT6 gene fusion. If systemic treatment is necessary, oncologists typically use other approaches, such as anti-angiogenic medications that starve the tumor of its blood supply.
How does the NAB2-STAT6 fusion cause a tumor to grow?
When these two genes fuse, the 'on switch' of the STAT6 gene gets stuck to the 'off switch' of the NAB2 gene. This abnormal combination creates a permanent 'on' signal that continuously tells the cell to divide and grow, eventually forming a tumor.

Questions for Your Doctor

  • • Did my pathology report show positive nuclear STAT6 staining, confirming my diagnosis?
  • • Was genomic sequencing performed to look for the specific gene fusion variant or any other mutations?
  • • Are there other features in my tumor biopsy, such as a high mitotic rate, that indicate a higher risk of the tumor growing quickly?
  • • If my tumor needs medical treatment, what systemic therapies do you recommend given that there are no therapies directly targeting this fusion?

Questions for You

  • • What did my doctor explain to me about my pathology report, and do I have a physical copy for my own records?
  • • Have I experienced any symptoms that initially led to the biopsy or surgical removal of this tumor?
  • • How comfortable do I feel asking my doctor to explain the medical terms in my pathology report?

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References

  1. 1

    FNA cytology of solitary fibrous tumors and the diagnostic value of STAT6 immunocytochemistry.

    Tani E, Wejde J, Åström K, et al.

    Cancer cytopathology 2018; (126(1)):36-43 doi:10.1002/cncy.21923.

    PMID: 28914981
  2. 2

    Establishment and characterization of NCC-SFT1-C1: a novel patient-derived cell line of solitary fibrous tumor.

    Iwata S, Noguchi R, Oosaki J, et al.

    Human cell 2025; (38(2)):49 doi:10.1007/s13577-025-01175-1.

    PMID: 39904835
  3. 3

    Adenofibromatous Solitary Fibrous Tumor: An Unusual Morphologic Variant Occurring in the Sinonasal Tract.

    Kwok ALM, Chan JKC, Tang AHN, et al.

    Head and neck pathology 2023; (17(1)):165-171 doi:10.1007/s12105-022-01490-1.

    PMID: 36166160
  4. 4

    Solitary Fibrous Tumor in the Retroperitoneal Space Arising from the Diaphragm.

    Seito T, Kaneko T, Kawai T, et al.

    In vivo (Athens, Greece) 2023; (37(6)):2849-2853 doi:10.21873/invivo.13401.

    PMID: 37905637
  5. 5

    Clinical and molecular implications of NAB2-STAT6 fusion variants in solitary fibrous tumour.

    Georgiesh T, Namløs HM, Sharma N, et al.

    Pathology 2021; (53(6)):713-719 doi:10.1016/j.pathol.2020.11.010.

    PMID: 33745702
  6. 6

    NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors.

    Hill CM, Indeglia A, Picone F, et al.

    bioRxiv : the preprint server for biology 2024; doi:10.1101/2024.04.15.589533.

    PMID: 38659891
  7. 7

    NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in solitary fibrous tumors.

    Hill C, Indeglia A, Picone F, et al.

    eLife 2025; (13()).

    PMID: 40875449
  8. 8

    NAB2-STAT6 fusion protein mediates cell proliferation and oncogenic progression via EGR-1 regulation.

    Park YS, Kim HS, Kim JH, et al.

    Biochemical and biophysical research communications 2020; (526(2)):287-292 doi:10.1016/j.bbrc.2020.03.090.

    PMID: 32216968
  9. 9

    Hippo signalling pathway mediates oncogenic properties of NAB2::STAT6 in solitary fibrous tumour.

    Salguero-Aranda C, Lobo-Selma L, Beltrán-Povea A, et al.

    Cellular oncology (Dordrecht, Netherlands) 2026; (49(1)):43 doi:10.1007/s13402-026-01173-x.

    PMID: 41665771
  10. 10

    Are bone erosion and peripheral feeding vessels hallmarks of intracranial solitary fibrous tumor/hemangiopericytoma?

    Sugiyama H, Tsutsumi S, Hashizume A, et al.

    Radiology case reports 2022; (17(8)):2702-2707 doi:10.1016/j.radcr.2022.04.050.

    PMID: 35669225
  11. 11

    Clinical and Radiographic Features for Differentiating Solitary Fibrous Tumor/Hemangiopericytoma From Meningioma.

    Ohba S, Murayama K, Nishiyama Y, et al.

    World neurosurgery 2019; (130()):e383-e392 doi:10.1016/j.wneu.2019.06.094.

    PMID: 31233926
  12. 12

    [Two Cases of Primary Intracranial Solitary Fibrous Tumor:Genetic Examination of NAB2-STAT6 Fusion and Its Association with Hemangiopericytoma].

    Kikuchi A, Fujita T, Takahashi Y, et al.

    No shinkei geka. Neurological surgery 2015; (43(7)):641-8 doi:10.11477/mf.1436203090.

    PMID: 26136329
  13. 13

    Recurrent Hypoglycemia in a Non-diabetic Female: A Case Study on Doege-Potter Syndrome.

    Mohammed SR, Mack N, Ramoutar V, Rampersad J

    Cureus 2024; (16(6)):e63329 doi:10.7759/cureus.63329.

    PMID: 39077286
  14. 14

    NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors.

    Tai HC, Chuang IC, Chen TC, et al.

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2015; (28(10)):1324-35 doi:10.1038/modpathol.2015.90.

    PMID: 26226844
  15. 15

    Molecular characterization of a series of solitary fibrous tumors, including immunohistochemical expression of STAT6 and NATB2-STAT6 fusion transcripts, using Reverse Transcriptase(RT)-Polymerase chain reaction(PCR) technique: An Indian experience.

    Rekhi B, Shetty O, Tripathi P, et al.

    Pathology, research and practice 2017; (213(11)):1404-1411 doi:10.1016/j.prp.2017.08.011.

    PMID: 28869107
  16. 16

    Intracranial anaplastic solitary fibrous tumor/hemangiopericytoma: immunohistochemical markers for definitive diagnosis.

    Yamashita D, Suehiro S, Kohno S, et al.

    Neurosurgical review 2021; (44(3)):1591-1600 doi:10.1007/s10143-020-01348-6.

    PMID: 32671693
  17. 17

    Intracranial solitary fibrous tumor/ hemangiopericytoma with osteoclast-like multinucleated giant cells: comparison with giant cell-rich solitary fibrous tumor.

    Vizcaíno MA, Bishop J, Sharma R, et al.

    Clinical neuropathology 2016; (35(4)):171-7 doi:10.5414/NP300933.

    PMID: 27049065
  18. 18

    Identification of BET inhibitors (BETi) against solitary fibrous tumor (SFT) through high-throughput screening (HTS).

    Mondaza-Hernandez JL, Moura DS, Li Y, et al.

    Neoplasia (New York, N.Y.) 2025; (70()):101244 doi:10.1016/j.neo.2025.101244.

    PMID: 41166819
  19. 19

    A Rare Metastatic Fibrous Tumor: Review of Literature With a Case Report.

    Swaminathan G, Muratori J, Rauf F, et al.

    JTO clinical and research reports 2025; (6(12)):100901 doi:10.1016/j.jtocrr.2025.100901.

    PMID: 41399740
  20. 20

    Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor.

    Schuetze SM, Bolejack V, Choy E, et al.

    Cancer 2017; (123(1)):90-97 doi:10.1002/cncr.30379.

    PMID: 27696380
  21. 21

    STAT6-targeting antisense oligonucleotides against solitary fibrous tumor.

    Li Y, Mondaza-Hernandez JL, Moura DS, et al.

    Molecular therapy. Nucleic acids 2024; (35(2)):102154 doi:10.1016/j.omtn.2024.102154.

    PMID: 38511173

This page explains the NAB2-STAT6 gene fusion for educational purposes only. Always consult your oncologist and pathologist to help interpret your specific pathology report and diagnosis.

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