Language
English
Publication Date
9-25-2025
Journal
Journal of the National Cancer Institute
DOI
10.1093/jnci/djaf278
PMID
40996338
PMCID
PMC12702491
PubMedCentral® Posted Date
12-15-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Osteosarcoma, the most common childhood bone tumor, can occur in rare cancer predisposition syndromes; however, most cases are sporadic with no known predisposing factors. We investigated the frequency of SMARCAL1 putative pathogenic variants in our large ongoing study of 2,119 osteosarcoma cases, their relation to patient characteristics, and the population prevalence. Our analysis uncovered a higher frequency of SMARCAL1 pathogenic variants across three osteosarcoma case sets (1.8%, n = 2,119) than in 2,625 comparably sequenced cancer-free controls (0.3%; P < .001). Cases with SMARCAL1 pathogenic variants had significantly improved overall survival compared to cases without these variants (hazard ratio 0.36, 95% CI 0.14-0.96, 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.
Keywords
SMARCAL1, germline genetics, osteosarcoma, pathogenic mutations
Published Open-Access
yes
Recommended Citation
Rafati, Maryam; Guenther, Lillian M; Egolf, Laura E; et al., "SMARCAL1 Is a New Osteosarcoma Predisposition Gene" (2025). Faculty, Staff and Students Publications. 6379.
https://digitalcommons.library.tmc.edu/baylor_docs/6379