(P 154) BCOR-MUTATED CONVENTIONAL AND DEDIFFERENTIATED CHONDROSARCOMA: A CLINICOPATHOLOGIC STUDY

Objective: Chondrosarcomas (CSAs) are a heterogeneous group of malignant neoplasms that arise within or on the surface of bone.
IDH1/2,  COL2A1, and TP53  are the most commonly mutated genes in conventional chondrosarcomas (CCSA) and dedifferentiated chondrosarcomas (DCSA).
Mutations in BCOR are frequently acquired in other IDH-driven neoplasms, and it is unclear if they contribute to IDH inhibitor resistance and disease progression.
The significance of BCOR mutations in CCSA and DCSA has not yet been defined.
After identifying an index case of CCSA with unusually aggressive clinical evolution, we investigated a series of BCOR-mutated CCSA and DCSA to determine the biological significance of this genetic alteration in these sarcoma subtypes.

Methods: We interrogated the surgical pathology archives for CCSA and DCSA between 2019 and 2023 that underwent genomic analysis to identify those with BCOR mutations.
All cases were sequenced using a commercial NGS panel (CARIS Life Sciences, Irving, Texas).
Fifteen in-house cases with available NGS results, were used as the group control.
Frequentist statistics were performed to establish association between the presence of BCOR mutations and mean tumor size, presence of metastases at diagnosis, dedifferentiation, histological grade, axial vs appendicular involvement, and pT stage (simplified as T1, T2, T3 and T4).

Results: The overall prevalence of BCOR mutations in CCSA and DCSA was 5% (12/231).
The mean size difference between the BCOR-mutated CSA group and the control group was 3.92 cm (p=0.024 CI=0.59-7.24), and the proportion difference for the presence of metastatic disease at the time of diagnosis was 0.42 (p= < 0.001). The proportion difference for having a pT stage3-4 vs 1-2 was 0.34 (p=0.009).
There were no statistically significant differences for histological grades, dedifferentiation, or involvement of axial skeleton or pT stage as a continuous variable.

Conclusion: This is the first study to establish the biological significance of BCOR mutations in CCSA and DCSA.
BCOR mutations are infrequent and can occur as standalone mutations or, most commonly, as co-occurring with other driver mutations.
Missense and frameshift mutations of BCOR are the genetic alterations in CCSA and DCSA without internal tandem duplication or rearrangements as in other sarcoma types.
BCOR mutations in CCSA and DCSA are associated with a larger tumor size, presence of metastasis at diagnosis, and higher pT category.

Clinicopathological findings and relevant statistical analysis results