Sargen Michael R, Kim Jung, Haley Jeremy S, Barker Hayley P, Mundra Piyushkumar A, Ballinger Mandy L, Thomas David M, Carey David J, Goldstein Alisa M, Stewart Douglas R
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Department of Genomic Health, Geisinger Clinic, Geisinger Health System, Danville, PA.
Genet Med Open. 2024 Sep 28;2:101895. doi: 10.1016/j.gimo.2024.101895. eCollection 2024.
To identify candidate susceptibility genes for dermatofibrosarcoma protuberans (DFSP).
All individuals with DFSP from the International Sarcoma Kindred Study ( = 3767 individuals with sarcoma diagnoses from Australia, Europe, New Zealand, and United States) and cohorts that were not ascertained based on sarcoma status or other phenotypes (Geisinger MyCode, = 170,503 individuals, United States; UK Biobank, = 469,789 individuals, United Kingdom) were evaluated for germline pathogenic or likely pathogenic (P/LP) variants in 156 cancer genes.
There were 92 unrelated individuals with DFSP across the 3 cohorts. The mean age at diagnosis (standard deviation) in the International Sarcoma Kindred Study, Geisinger, and UK Biobank was 40.8 (14.5), 50.3 (9.4), and 49.4 (13.2) years, respectively. Germline P/LP variants were most common in the gene (4/92 [4.3%]). related cases were often associated with early onset disease (age at diagnosis: 30-39 years) and were observed in all 3 cohorts. Among 640,292 individuals in Geisinger and UK Biobank who were not ascertained based on phenotype, there was a significantly increased frequency of P/LP variants among individuals with DFSP ( = 3/65 [4.6%]) compared to those without ( = 6388/640,227 [1.0%]) (Fisher exact, = .03). Additional genes with P/LP variation (1 case for each gene) included and .
This study of multiple cohorts identifies as a candidate susceptibility gene for DFSP. Additional epidemiologic and functional studies are needed to further characterize this potential gene-tumor relationship.
鉴定隆突性皮肤纤维肉瘤（DFSP）的候选易感基因。
对国际肉瘤家系研究（来自澳大利亚、欧洲、新西兰和美国的3767例肉瘤诊断患者）以及未根据肉瘤状态或其他表型确定的队列（美国盖辛格MyCode研究，170503例个体；英国生物银行，469789例个体）中的所有DFSP患者，评估156个癌症基因中的种系致病性或可能致病性（P/LP）变异。
3个队列中有92例无关的DFSP患者。国际肉瘤家系研究、盖辛格研究和英国生物银行中患者的诊断平均年龄（标准差）分别为40.8（14.5）岁、50.3（9.4）岁和49.4（13.2）岁。种系P/LP变异在该基因中最为常见（4/92 [4.3%]）。相关病例常与早发性疾病相关（诊断年龄：30 - 39岁），且在所有3个队列中均有观察到。在盖辛格研究和英国生物银行中未根据表型确定的640292例个体中，DFSP患者中该基因P/LP变异的频率（3/65 [4.6%]）显著高于无DFSP的个体（6388/640227 [1.0%]）（Fisher精确检验，P = 0.03）。具有P/LP变异的其他基因（每个基因1例）包括[具体基因名称缺失]和[具体基因名称缺失]。
这项对多个队列的研究确定该基因是DFSP的候选易感基因。需要进一步的流行病学和功能研究来进一步阐明这种潜在的基因 - 肿瘤关系。
