Identification Of Actionable Genetic Targets In Primary Cardiac Sarcomas

• Main Authors: Salvador-Coloma C, Saigí M, Díaz-Beveridge R, Penín RM, Pané-Foix M, Mayordomo E, Melián M, Schuler M, García Del Muro X, Font de Mora J
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-11-01
• Series: OncoTargets and Therapy
• Subjects: primary cardiac sarcomas; molecular karyotype; actionable genes.
• Online Access: https://www.dovepress.com/identification-of-actionable-genetic-targets-in-primary-cardiac-sarcom-peer-reviewed-article-OTT
• ISSN: 1178-6930

Carmen Salvador-Coloma,1,2,* María Saigí,3,* Roberto Díaz-Beveridge,1 Rosa María Penín,4 María Pané-Foix,4 Empar Mayordomo,5 Marcos Melián,1 Mona Schuler,6 Xavier García Del Muro,3 Jaime Font de Mora2 1Department of Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 2Laboratory of Cellular and Molecular Biology, Clinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; 3Department of Medical Oncology, Institut Català Oncologia, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; 4Department of Pathology, Hospital Universitari de Bellvitge, Barcelona, Spain; 5Department of Pathology, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 6Department of Cardiac Surgery, Hospital Universitari i Politècnic La Fe, Valencia, Spain*These authors contributed equally to this workCorrespondence: Carmen Salvador-ColomaJaime Font de Mora Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Torre A, 5-07, Valencia 46026 SpainTel [phone]Email [e-mail]: Primary cardiac tumors are extremely rare; most are myxomas with a benign prognosis. However, primary sarcomas are highly aggressive and treatment options are limited. Radical surgery is often not feasible and conventional therapies provide only modest results. Due to the rare nature of primary cardiac tumors, there are no proper randomized studies to guide treatment. Their complexity requires alternative approaches in order to improve treatment efficacy.Methods: We isolated DNA from 5 primary cardiac sarcomas; the quality of DNA from 3 of them was sufficient to perform high-resolution single nucleotide polymorphism (SNP) array analysis.Results: In the present study, molecular karyotyping revealed numerous segmental chromosomal alterations and amplifications affecting actionable genes that may be involved in disease initiation and/or progression. These include chromosomal break flanking AKT2 in undifferentiated pleomorphic rhabdomyosarcoma, chromosomal break in promoter of TERT, and gain of CDK4 and amplification of MDM2 in inflammatory myofibroblastic tumor. We detected segmental break flanking MOS in high-grade myxofibrosarcoma. In addition, the high number of chromosomal aberrations in high-grade myxofibrosarcoma may cause multiple tumor-specific epitopes, supporting the study of immunotherapy treatment in this type of aggressive tumor.Conclusion: Our results provide a genetic rationale that supports an alternative, personalized therapeutic management of primary cardiac sarcomas.Keywords: primary cardiac sarcomas, molecular karyotype, actionable genes