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Updated: Jan 17, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
SMARCAL1 is a new osteosarcoma predisposition gene
Maryam Rafati1, Lillian M Guenther2, Laura E Egolf1,3
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850-9772, United States.
Abstract:
Osteosarcoma, the most common childhood bone tumor, can occur in rare cancer predisposition syndromes; however, most are sporadic with no known predisposing factors. We investigated the frequency of SMARCAL1 putative pathogenic variants in our large ongoing study of 2119 osteosarcoma patients, their relation to patient characteristics, and the population prevalence. Our analysis uncovered a higher frequency of SMARCAL1 pathogenic variants across 3 osteosarcoma patient sets (1.8%, n = 2119) than in 2625 comparably sequenced cancer-free individuals (0.3%; P < .001). Patients with SMARCAL1 pathogenic variants had statistically significantly improved overall survival compared with patients without these variants (hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.14 to 0.96; P = .034). In the UK Biobank (469 557 exomes), there was a 33-fold increased risk of osteosarcoma in individuals with SMARCAL1 pathogenic variants. These results identify SMARCAL1 as a new osteosarcoma predisposition gene and thus warrant follow-up to identify the mechanisms by which SMARCAL1 contributes to the etiology of osteosarcoma.
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