Ewing sarcoma and CHEK2-related tumor predisposition syndrome (case report and review)

Ewing sarcoma is a relatively rare aggressive tumor of bones and soft tissues characterized by specific chromosomal translocations involving genes and transcription factors of the FET and ETS families. A number of studies have demonstrated the presence of molecular genetic events preceding these specific rearrangements.
The article presents a clinical observation of the treatment of a 24-year-old patient with Ewing sarcoma of the X rib and CHEK2-associated cancer predisposition syndrome with an oncologically burdened family history, including Ewing sarcoma in a first-degree relative. Specific translocation of the EWSR1 gene (22q12) was identified, characteristic of tumors of the Ewing sarcoma/PNET (primitive neuroectodermal tumors) family, as well as 59 variants of different functional significance in suppressor genes and driver genes was identified in the course of a comprehensive molecular genetic study using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) with a targeted custom panel including 415 genes involved in carcinogenesis. The patient underwent combined treatment in the volume of neoadjuvant polychemotherapy, surgical stage (extirpation of the X rib with plastic surgery) and subsequent adjuvant polychemotherapy. During dynamic observation for the period 2022–2025, there were no signs of progression and metastatic process. 
Molecular genetic profiling in Ewing sarcoma has identified markers that may act as risk modifiers for disease development and progression, determine sensitivity/resistance to standard treatment methods, and serve as potential targets for personalized treatment.

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