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 MDM2, CDK4, PDGFRA, and NOTCH2, as well as copy number losses in CDKN2A and CDKN2B. Actionable alterations included mutations in ATM/ATR, PTCH1, and
PDGFRB. Moreover, genomic rearrangement events, specifically PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions were identified. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion positive
tumor and
PDGFRB mutations in both fusion-positive cases. Our study suggests that
PDGFRB 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.