背景:颅面骨肉瘤(CFOS)是头颈部罕见的恶性肿瘤,临床表现不同,长骨骨肉瘤的生物学行为和预后。在CFOS上发表的遗传数据非常有限。
方法:在目前的研究中,我们通过SNP阵列和靶向下一代测序对15例高级别CFOS进行了全面的基因组研究.
结果:我们的研究表明,高级CFOS表现出高度复杂和异质性的基因组改变,并带有频繁突变的肿瘤抑制基因TP53,CDKN2A/B,和PTEN,类似于传统的骨肉瘤。潜在可操作的基因扩增涉及CCNE1,AKT2,MET,NTRK1,PDGFRA,KDR,KIT,43%的病例可见MAP3K14,FGFR1和AURKA。在CFOS病例的一部分中也发现了GNAS热点激活突变,一例代表纤维发育不良的恶变,提示GNAS突变在CFOS发育中的作用。
结论:高级CFOS表现出高度复杂和异质性的基因组改变,涉及受体酪氨酸激酶基因的扩增,和涉及肿瘤抑制基因的频繁突变。
BACKGROUND: Craniofacial osteosarcomas (CFOS) are uncommon malignant neoplasms of the head and neck with different clinical presentation, biological behavior and prognosis from conventional osteosarcomas of long bones. Very limited genetic data have been published on CFOS.
METHODS: In the current study, we performed comprehensive genomic studies in 15 cases of high-grade CFOS by SNP array and targeted next generation sequencing.
RESULTS: Our study shows high-grade CFOS demonstrate highly complex and heterogenous genomic alterations and harbor frequently mutated tumor suppressor genes TP53, CDKN2A/B, and PTEN, similar to conventional osteosarcomas. Potentially actionable gene amplifications involving CCNE1, AKT2, MET, NTRK1, PDGFRA, KDR, KIT, MAP3K14, FGFR1, and AURKA were seen in 43% of cases. GNAS hotspot activating mutations were also identified in a subset of CFOS cases, with one case representing malignant transformation from fibrous dysplasia, suggesting a role for GNAS mutation in the development of CFOS.
CONCLUSIONS: High-grade CFOS demonstrate highly complex and heterogenous genomic alterations, with amplification involving receptor tyrosine kinase genes, and frequent mutations involving tumor suppressor genes.