Harnessing AACR Project GENIE to Define the Molecular Features of Desmoplastic Small Round Cell Tumor

Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive soft tissue sarcoma of the abdomen. With an asymptomatic course and rapid dissemination, DSRCT’s prognosis is poor at diagnosis. This study characterizes the demographic variation and genomic profile of DSRCT to guide studies into diagnosis and treatment. The AACR GENIE database was utilized to identify genetic alterations in DSRCT. Data was queried to identify disease prevalence by different demographic variables. Information was collected on frequency of somatic mutations and copy number alterations, rates of mutation co-occurrence, and mutations seen in primary and metastatic samples. ARID1A, TP53, ATM, TERT, and FGFR4 were the most frequently identified somatic mutations. Copy number alterations seen in DSRCT were commonly homozygous deletions in tumor suppressor genes. Independent of sex, WT1 mutations were most common. Non-White patients saw single occurrences of many mutations but recurrent ones in ANKRD11 and KMT2C. Co-occurrence was found between FGFR4 and EP300. Moreover, primary tumor samples had exclusive mutations in AKAP9, KDM2B, MAGED1, MKI67, PCLO, and TRAF1. Metastatic samples had exclusive mutations in FIP1L1 and NRIP1. Our data highlights mutational variation across demographic cohorts. These patterns are vital to future studies into identifying diagnostic markers or therapeutic targets.