Genomic profiling of sarcomas: a promising weapon in the therapeutic arsenal

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 14227
• Main Authors: Lopes Brás, Raquel, López Presa, María Dolores, Esperança Martins, Miguel, Melo Alvim, Cecilia, Gallego Páez, Lina Marcela, Costa, Luis, Fernandes, Isabel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 17-11-2022; MDPI AG
• Subjects: Cancer care; Cell cycle; Chemotherapy; Comprehensive genomic profiling; Deoxyribonucleic acid; DNA; Drug delivery; Drugs; Ewings sarcoma; Genes; Genetic Profile; Genomics; Growth factors; Humans; MDM2 protein; Medical prognosis; Mesenchyme; Mutation; Myc protein; Neoplasms; Next-generation sequencing; p53 Protein; Patients; Radiation therapy; Rare tumor; Retrospective Studies; Sarcoma; Sarcoma - drug therapy; Sarcoma - genetics; sarcoma sequencing-directed therapy; Soft Tissue Neoplasms; Targeted therapy; Tumors; cancer care; targeted therapy; rare tumor; next-generation sequencing; sarcoma sequencing-directed therapy; comprehensive genomic profiling; genomics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232214227

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Sarcomas are rare malignant mesenchymal neoplasms, and the knowledge of tumor biology and genomics is scarce. Chemotherapy is the standard of care in advanced disease, with poor outcomes. Identifying actionable genomic alterations may offer effective salvage therapeutic options when previous lines have failed. Here, we report a retrospective cohort study of sarcoma patients followed at our center and submitted to comprehensive genomic profiling between January 2020 and June 2021. Thirty patients were included, most (96.7%) with reportable genomic alterations. The most common alterations were linked to cell cycle regulation (TP53, CDKN2A/B, and RB1 deletions and CDK4, MDM2, and MYC amplifications). Most patients (96.7%) had microsatellite stability and low tumor mutational burden (≤10 muts/megabase (Mb); median 2 Muts/Mb). Two-thirds of patients had actionable mutations for targeted treatments, including five cases with alterations amenable to targeted therapies with clinical benefit within the patient's tumor type, ten cases with targetable alterations with clinical benefit in other tumor types, and five cases with alterations amenable to targeting with drugs under investigation in a clinical trial setting. A significant proportion of cases in this study had actionable genomic alterations with available targeted drugs. Next-generation sequencing is a feasible option for identifying molecular drivers that can provide therapeutic options for individual patients. Molecular Tumor Boards should be implemented in the clinical practice to discuss genomic findings and inform clinically relevant targeted therapies.