| Title: | SMARCAL1 is a new osteosarcoma predisposition gene |
| Journal: | Journal of the National Cancer Institute |
| Published: | 25 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40996338/ |
| DOI: | https://doi.org/10.1093/jnci/djaf278 |
| URL: | https://pmc.ncbi.nlm.nih.gov/articles/PMC12702491/ |
Publication 19413
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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.</p>
39 Authors
- Maryam Rafati
- Lillian M Guenther
- Laura E Egolf
- Matthew Gianferante
- Jung Kim
- Kevin Wang
- Bin Zhu
- Logan G Spector
- Nathan Anderson
- Katherine A Janeway
- Donald A Barkauskas
- Douglas S Hawkins
- Ana Patiño-Garcia
- Philip J Lupo
- Michael E Scheurer
- Lindsay Morton
- Gregory T Armstrong
- Yadav Sapkota
- M Monica Gramatges
- Massimo Serra
- Claudia Hattinger
- Katia Scotlandi
- Irene L Andrulis
- Jay S Wunder
- Mandy L Ballinger
- David M Thomas
- Meredith Yeager
- Michael Dean
- Douglas R Stewart
- Aurelie Vogt
- Jia Liu
- Belynda D Hicks
- Wen-Yi Huang
- Maria Teresa Landi
- Adriana Lori
- W Ryan Diver
- Sharon A Savage
- Stephen J Chanock
- Lisa Mirabello
1 Application
| Application ID | Title |
|---|---|
| 54389 | Frequency, phenotypic spectrum, and penetrance of pathogenic variation in cancer susceptibility genes in the general population |
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