NAB2 and Solitary Fibrous Tumor

This summary outlines the strong association between NAB2 (HGNC:7627) and solitary fibrous tumor (MONDO_0016238). Multiple independent studies have consistently identified a NAB2-STAT6 fusion in solitary fibrous tumors, where NAB2 rearrangements appear as a recurrent molecular event. Case reports have documented these gene fusions in tumors arising in diverse locations including the kidney and the head and neck, thus reinforcing the diagnostic significance of the fusion (PMID:26337721).

Clinical evidence spans both single-patient case reports and multi‐patient studies. In several reports, NAB2-STAT6 fusion events were detected by reverse transcription-PCR, direct sequencing, and in situ assays. Multi‐patient analyses report that up to 92% of solitary fibrous tumor cases harbor these recurrent fusions, with distinct fusion breakpoint patterns correlating with tumor location and aggressiveness (PMID:24513261).

Genetic evidence is underscored by the reproducible identification of NAB2-STAT6 gene fusions and the detection of multiple fusion variants. The genetic alterations typically involve a truncation in NAB2 and through fusion create chimeric proteins with aberrant function. Although a specific coding variant in NAB2 in HGVS format was not explicitly provided in these studies, the consistent molecular findings across independent cohorts lend strong support to the genetic basis of the association (PMID:26226844).

Functional assessments further cement the role of NAB2-STAT6 fusions in tumorigenesis. Immunohistochemical analyses routinely demonstrate strong nuclear STAT6 expression which is mechanistically linked to the fusion event. These functional studies, while not exhaustive in documenting rescue experiments, provide evidence that the fusion alters transcriptional regulation consistent with the tumor phenotype (PMID:24513261).

No conflicting evidence currently disputes this association, as alternative explanations for solitary fibrous tumor pathogenesis have been less robust compared to the fusion data. Moreover, while some heterogeneity exists in fusion variant types, the overall picture continues to support a unified molecular diagnostic criterion.

In summary, the integrated clinical, genetic, and functional evidence robustly ties NAB2 to the oncogenesis of solitary fibrous tumor. This association not only assists in diagnostic decision‑making but also informs risk stratification and targeted approaches in future publications.

Key Take‑Home: Recurrent NAB2-STAT6 fusions serve as a critical molecular hallmark in solitary fibrous tumors, enhancing diagnostic precision and guiding clinical management.

References

• Diagnostic pathology • 2015 • A GRIA2 and PAX8-positive renal solitary fibrous tumor with NAB2-STAT6 gene fusion PMID:26337721
• Auris, nasus, larynx • 2020 • Spinal solitary fibrous tumor of the neck: Next-generation sequencing-based analysis of genomic aberrations PMID:31879078
• Virchows Archiv • 2020 • Solitary fibrous tumor: a case series identifying pathological adverse factors‑implications for risk stratification and classification PMID:31529158
• The American journal of pathology • 2014 • Solitary fibrous tumors/hemangiopericytomas with different variants of the NAB2-STAT6 gene fusion are characterized by specific histomorphology and distinct clinicopathological features PMID:24513261
• Modern pathology • 2015 • NAB2‑STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors PMID:26226844

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