Clinico-Genomic Profiling of Conventional and Dedifferentiated Chondrosarcomas Reveals TP53 Mutation to Be Associated with Worse Outcomes

Ryan A Denu 1, Richard K Yang 2, Alexander J Lazar 2 3, Shalin S Patel 4, Valerae O Lewis 4, Jason Roszik 5, J Andrew Livingston 1, Wei-Lien Wang 2, Kenna R Shaw 6, Ravin Ratan 1, Maria A Zarzour 1, Justin Bird 4, Shaan Raza 7, Kadir C Akdemir 7, Jordi Rodon Ahnert 8, Vivek Subbiah 8, Shreyaskumar Patel 1, Anthony P Conley 1

Purpose: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes.

Experimental design: We included 93 patients with conventional and dedifferentiated chondrosarcoma for which there were available clinical next-generation sequencing data. Clinical and genomic data were extracted and compared between IDH mutant and IDH WT chondrosarcomas and between TP53 mutant and TP53 WT chondrosarcomas.

Results: IDH1 and IDH2 mutations are prevalent in chondrosarcoma (50.5%), more common in chondrosarcomas arising in the extremities, associated with higher age at diagnosis, and more common in dedifferentiated chondrosarcomas compared with grades 1-3 conventional chondrosarcoma. There was no difference in survival based on IDH mutation in univariate and multivariate analyses. TP53 mutation was the next most prevalent (41.9%) and is associated with worse overall survival and metastasis-free survival in both univariate and multivariate analyses. TP53 mutation was also associated with higher risk of recurrence following curative-intent surgery and worse survival among patients that presented with de novo metastatic disease.

Conclusions: IDH mutations are prevalent in chondrosarcoma though were not associated with survival outcomes in this cohort. TP53 mutations were the next most common alteration and were associated with worse outcomes.

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©2023 American Association for Cancer Research.

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