DNA Mutational and Copy Number Variation Profiling of Primary Craniofacial Osteosarcomas by Next-Generation Sequencing.

IF 3.2 Q2 PATHOLOGY Head & Neck Pathology Pub Date : 2024-06-17 DOI:10.1007/s12105-024-01634-5

Gord Guo Zhu, Chuanyong Lu, Ivana Petrovic, Khedoudja Nafa, Wen Chen, Aijazuddin Syed, Satshil Rana, Michael J Klein, Sinchun Huang, Lu Wang, William D Tap, Ronald A Ghossein, Jatin Shah, Meera R Hameed

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Abstract

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.

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利用新一代测序技术分析原发性颅面骨肉瘤的DNA突变和拷贝数变异情况

背景：颅面骨肉瘤（CFOS）是头颈部不常见的恶性肿瘤，其临床表现、生物学行为和预后与传统的长骨骨肉瘤不同。有关 CFOS 的遗传学数据非常有限：在本研究中，我们通过 SNP 阵列和靶向新一代测序对 15 例高级别 CFOS 进行了全面的基因组研究：结果：我们的研究显示，高级别CFOS表现出高度复杂和异质性的基因组改变，并携带频繁突变的肿瘤抑制基因TP53、CDKN2A/B和PTEN，与传统骨肉瘤相似。43%的病例存在潜在的可操作基因扩增，包括CCNE1、AKT2、MET、NTRK1、PDGFRA、KDR、KIT、MAP3K14、FGFR1和AURKA。在一部分CFOS病例中还发现了GNAS热点激活突变，其中一例是由纤维发育不良恶性转化而来，这表明GNAS突变在CFOS的发病过程中发挥了作用：结论：高级别CFOS表现出高度复杂和异质性的基因组改变，受体酪氨酸激酶基因扩增，抑癌基因突变频繁。

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来源期刊

Head & Neck Pathology PATHOLOGY-

CiteScore

5.70

自引率

9.50%

发文量

期刊介绍： Head & Neck Pathology presents scholarly papers, reviews and symposia that cover the spectrum of human surgical pathology within the anatomic zones of the oral cavity, sinonasal tract, larynx, hypopharynx, salivary gland, ear and temporal bone, and neck. The journal publishes rapid developments in new diagnostic criteria, intraoperative consultation, immunohistochemical studies, molecular techniques, genetic analyses, diagnostic aids, experimental pathology, cytology, radiographic imaging, and application of uniform terminology to allow practitioners to continue to maintain and expand their knowledge in the subspecialty of head and neck pathology. Coverage of practical application to daily clinical practice is supported with proceedings and symposia from international societies and academies devoted to this field. Single-blind peer review The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.