Clinical relevance of BCOR internal tandem duplication and TP53 aberration in clear cell sarcoma of the kidney

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal malig-nancy, characterized by BCOR internal tandem duplication (ITD), YWHAE rearrangement, BCOR-CCNB3 fusion, and lack of other consistent structural alteration. We accidentally identified TP53 dele-tion in CCSK, which was often associated with adverse clinical outcomes. In this study, we assessed the incidence as well as the clinical relevance of these molecules in CCSK patients. BCOR ITD, YWHAE rearrangement, BCOR-CCNB3 fusion and TP53 status were examined by polymerase chain reaction, fluorescence in situ hybridization, or Sanger sequencing in a cohort of 39 patients with CCSK. Among them, 34 cases (87.18%) had BCOR ITD, 1 (2.56%) had YWHAE rearrangement, and 1 (2.56%) had BCOR-CCNB3 gene fusion. The remaining 3 (7.69%) harbored none of these aberrations. BCOR ITD, YWHAE rearrangement and BCOR-CCNB3 were mutually exclusive. Further-more, 25.64% of the cohort acquired TP53 aberration (10/39, 3 with both copy number deletion and point mutation, 6 with deletion only, and 1 with mutation only), all of which were associated with BCOR ITD. Patients with or without BCOR ITD or TP53 aberration did not differ in demographic char-acteristics such as sex, onset age, or tumor stage at diagnosis. However, the overall survival rates and progression-free survival rates of BCOR ITD or TP53 deletion groups showed obvious downward trends, albeit not all reaching statistical significance. Patients with both BCOR ITD and TP53 deletion had the poorest prognosis.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Clear cell sarcoma of the kidney (CCSK) is often associated with TP53 deletion, which is related to adverse clinical outcomes. A study analyzed 39 CCSK patients and found that 87.18% of patients had BCOR internal tandem duplication (ITD), 2.56% had YWHAE rearrangement, and 2.56% had BCOR-CCNB3 gene fusion. Furthermore, 25.64% of patients had TP53 aberration, and patients with both BCOR ITD and TP53 deletion had the poorest prognosis.