Gene Fusion Patterns May Flag High Risk Solitary Fibrous Tumors

SFTs most commonly arise in the chest cavity but can also occur in the abdomen, pelvis, brain, and extremities. Their behavior is unpredictable, ranging from indolent lesions to rapidly recurrent or metastatic disease. 

Physicians currently use the Demicco score, based on patient age, tumor size, and microscopic appearance, to estimate SFT aggressiveness, but this approach can still leave uncertainty about which patients need closer surveillance. New findings show that specific genetic fusion patterns may add precision by helping identify SFTs more likely to recur or spread.

At Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine (Miami, FL, USA), investigators evaluated whether breakpoints within the NAB2-STAT6 fusion can function as biomarkers of aggressiveness. SFTs are defined by this genetic fusion, which occurs when two neighboring genes on chromosome 12 break apart and fuse back together at the wrong location. The study focused on defining the precise genomic junction within the fusion and determining whether breakpoint location could add prognostic information beyond established clinicopathologic scoring.

In a cohort of 48 SFT patients treated at Sylvester, researchers reviewed charts, outcomes, and molecular reports to test associations between breakpoint category and disease course. Although multiple fusion variants are known, the team grouped tumors into proximal and distal categories, with proximal breakpoints occurring closer to the beginning of the genes and distal breakpoints occurring farther downstream. This classification provided the analytic anchor for correlating fusion patterns with tumor behavior.

The analysis, conducted under The Horowitz Solitary Fibrous Tumor Initiative, will be presented in a rapid oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The study also explored anatomical distribution and recurrence patterns across fusion classes.

Patients with distal NAB2-STAT6 variants had a higher likelihood of metastatic spread, whereas none of the proximal-variant cases metastasized. Distal variants were more frequently located outside the chest cavity; these tumors were larger, more prone to recur, and exhibited more aggressive behavior.

The authors suggest that fusion variants may serve as prognostic and potentially predictive biomarkers, while emphasizing that the data remain preliminary and not yet practice-guiding. Ongoing efforts include international expansion of an SFT registry and the development of cell and preclinical models to interrogate variant biology and therapeutic response.

“This work is helping us move toward a more precision-based approach for these patients,” said Gina D’Amato, M.D., sarcoma medical oncologist at Sylvester. “Instead of patients cycling through many different therapies, our goal is to better understand which tumors are more aggressive and which treatments may work best based on the biology of the disease.”

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Sylvester Comprehensive Cancer Center