Genomic and transcriptomic characterization of desmoplastic small round cell tumors

Desmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue tumor primarily affecting children and young adults. Most cases display a pathognomonic EWSR1-WT1 gene fusion, presumably constituting the primary driver event. Little is, however, known about secondary genetic changes that may affect tumor progression. We here studied 25 samples from 19 DSRCT patients using single nucleotide polymorphism arrays and found that all samples had copy number alterations. The most common imbalances were gain of chromosomes/chromosome arms 1/1q and 5/5p and loss of 6/6q and 16/16q, all occurring in at least eight of the patients. Five cases showed homozygous deletions, affecting a variety of known tumor suppressor genes, for example, CDKN2A and NF1. As almost all patients died of their disease, the impact of individual imbalances on survival could not be evaluated. Global gene expression analysis using mRNA sequencing on fresh-frozen samples from seven patients revealed a distinct transcriptomic profile, with enrichment of genes involved in neural differentiation. Two genes - GJB2 and GAL - that showed higher expression in DSRCT compared to control tumors could be further investigated for their potential as diagnostic markers at the protein level.

Automated summary

Desmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue tumor primarily affecting children and young adults, with most cases displaying a pathognomonic gene fusion. Copy number alterations were found in all DSRCT patient samples, with common imbalances including gain of chromosomes/chromosome arms 1/1q and 5/5p and loss of 6/6q and 16/16q. Global gene expression analysis revealed a distinct transcriptomic profile with enrichment of genes involved in neural differentiation, and two genes, GJB2 and GAL, showed potential as diagnostic markers at the protein level in DSRCT.