SMARCAL1 is a new osteosarcoma predisposition gene

作者：Maryam Rafati, Lillian M. Guenther, Laura E. Egolf, D. Matthew Gianferante, Jung Kim, Kevin Wang, Bin Zhu, Logan G. Spector, Nathan Anderson, Katherine A. Janeway, Donald A. Barkauskas, Douglas S. Hawkins, Ana Patiño‐García, Philip J. Lupo, Michael E. Scheurer, Lindsay M. Morton, Gregory T. Armstrong, Yadav Sapkota, M. Monica Gramatges, Massimo Serra, Claudia Maria Hattinger, Katia Scotlandi, Irene L. Andrulis, Jay S. Wunder, Mandy L. Ballinger, David M Thomas, Meredith Yeager, Michael Dean, Douglas R. Stewart, Aurélie Vogt, Jia Liu, Belynda Hicks, Wen‐Yi Huang, Maria Teresa Landi, Adriana Lori, W Ryan Diver, Sharon A. Savage, Stephen J. Chanock, Lisa Mirabello · 发表于：JNCI Journal of the National Cancer Institute · 年份：2025 · DOI：10.1093/jnci/djaf278 · 被引用次数：3 · 研究领域：Peptidase Inhibition and Analysis、Chromatin Remodeling and Cancer、Cholangiocarcinoma and Gallbladder Cancer Studies

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.