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-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
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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. 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引用次数: 0
摘要
骨肉瘤是最常见的儿童骨肿瘤，可发生在罕见的癌症易感综合征中；然而，大多数病例是散发的，没有已知的诱发因素。在我们对2119例骨肉瘤病例进行的大型研究中，我们调查了SMARCAL1假定致病变异的频率，以及它们与患者特征和人群患病率的关系。我们的分析发现，在三个骨肉瘤病例组中，SMARCAL1致病性变异的频率（1.8%,n = 2,119）高于2,625个相同测序的无癌对照（0.3%,P < 0.001）。与没有SMARCAL1致病变异的患者相比，携带SMARCAL1致病变异的患者的总生存率显著提高（风险比0.36,95% CI 0.14-0.96, P = 0.034）。在英国生物银行（469,557个外显子组）中，携带SMARCAL1致病变异的个体患骨肉瘤的风险增加了33倍。这些结果表明SMARCAL1是一种新的骨肉瘤易感基因，因此需要进一步确定SMARCAL1在骨肉瘤病因学中的作用机制。
SMARCAL1 is a new osteosarcoma predisposition gene.
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.
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