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

期刊论文
发表日期：

2024年6月17日

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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

摘要

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.