Unique Aberrations in Intimal Sarcoma Identified by Next-Generation Sequencing as Potential Therapy Targets

Abstract

Intimal sarcomas are rare and histologically heterogeneous tumors, commonly arising from the pulmonary arteries. They have remained challenging to treat. Few studies in the literature study the genomics of this cancer. Identifying targetable alterations is an important step in advancing the treatment of intimal sarcomas. Using data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR GENIE) database, we cataloged genetic alterations and assessed their clinical utility from thirteen patients with intimal sarcoma. Notable copy number alterations included amplification in <i>MDM2</i>, <i>CDK4</i>, <i>PDGFRA</i>, and <i>NOTCH2</i>, as well as copy number losses in <i>CDKN2A</i> and <i>CDKN2B</i>. Actionable alterations included mutations in <i>ATM/ATR</i>, <i>PTCH1</i>, and <i>PDGFRB</i>. Moreover, genomic rearrangement events, specifically <i>PDE4DIP-NOTCH2</i> and <i>MRPS30-ARID2</i> fusions were identified. Co-occurring alterations included a <i>NOTCH2</i> copy number gain in the <i>PDE4DIP-NOTCH2</i> fusion positive tumor and <i>PDGFRB</i> mutations in both fusion-positive cases. Our study suggests that <i>PDGFRB</i> may be relevant in the tumorigenesis process. Including genomic profiling in the management of intimal sarcoma and potential enrollment in targeted therapy trials is warranted.