下一代测序技术对原发性颅面骨肉瘤的 DNA 突变和拷贝数变异进行分析。
DNA Mutational and Copy Number Variation Profiling of Primary Craniofacial Osteosarcomas by Next-Generation Sequencing.
机构信息
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Department of Pathology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ, 08103, USA.
出版信息
Head Neck Pathol. 2024 Jun 17;18(1):48. doi: 10.1007/s12105-024-01634-5.
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.
RESULT
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.
CONCLUSION
High-grade CFOS demonstrate highly complex and heterogenous genomic alterations, with amplification involving receptor tyrosine kinase genes, and frequent mutations involving tumor suppressor genes.
背景
颅面部骨肉瘤（CFOS）是一种罕见的头颈部恶性肿瘤，其临床表现、生物学行为和预后与长骨的常规骨肉瘤不同。关于 CFOS 的遗传数据非常有限。
方法
在本研究中，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，高级别 CFOS 表现出高度复杂和异质性的基因组改变，并经常发生肿瘤抑制基因 TP53、CDKN2A/B 和 PTEN 的突变，与常规骨肉瘤相似。在 43%的病例中，观察到涉及 CCNE1、AKT2、MET、NTRK1、PDGFRA、KDR、KIT、MAP3K14、FGFR1 和 AURKA 的潜在可操作基因扩增。在一部分 CFOS 病例中还发现了 GNAS 热点激活突变，其中一例代表纤维结构不良的恶性转化，提示 GNAS 突变在 CFOS 的发生发展中起作用。
结论
高级别 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，以及涉及肿瘤抑制基因的频繁突变。
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