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

Authors

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

Publication Date

12-1-2023

Journal

Clinical Cancer Research

Abstract

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.

Keywords

Adult, Humans, Mutation, Chondrosarcoma, Bone Neoplasms, Bone and Bones, Genomics, Isocitrate Dehydrogenase, Tumor Suppressor Protein p53, chondrosarcoma, genomics, IDH1, IDH2, TP53, TERT

DOI

10.1158/1078-0432.CCR-23-1703

PMID

37747813

PMCID

PMC10835757

PubMedCentral® Posted Date

12-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes