Pathol Res Pract. 2022 Feb 25. pii: S0344-0338(22)00063-2. [Epub ahead of print]232
153820
Elena Tirrò,
Federica Martorana,
Giovanni Micale,
Nicola Inzerilli,
Rosaria Carciotto,
Chiara Romano,
Claudio Longhitano,
Gianmarco Motta,
Katia Lanzafame,
Stefania Stella,
Michele Massimino,
Silvia Rita Vitale,
Lucia Salvatorelli,
Gaetano Magro,
Livia Manzella,
Paolo Vigneri.
Sarcomas are mesenchymal-derived cancers with overlapping clinical and pathologic features and a remarkable histological heterogeneity. While a precise diagnosis is often challenging to achieve, systemic treatment of sarcomas is still quite uniform. In this scenario, next generation sequencing (NGS) may be exploited to assist diagnosis and to identify specific targetable alterations. However, the precise role of genomic characterization in these diseases is still debated. In the present study, we analyzed 18 samples from 11 low-incidence sarcomas using NGS technology. We also used an in-silico prediction tool to reclassify variants of unknown significance and then looked for potentially druggable alterations to match with targeted therapies. Our cohort presented several predictable findings (e.g. MYC amplification in radio-induced angio-sarcoma, COL1A1-PDGFB rearrangements in dermatofibrosarcoma protuberans) along with unexpected results (e.g. the reciprocal WT1-EWSR1 fusion in a desmoplastic small round cell tumor). One third of patients (6/18) displayed at least one actionable molecular alterations. Our experience confirms the potential role of NGS in the management of rare sarcomas. This tool may support the diagnostic process, but also detect targets for personalized therapies.
Keywords: Molecular alterations; Next Generation Sequencing; Rare tumors; Sarcoma; Targeted Therapy