Fusion RNA profiling provides hints on cell of origin of mysterious tumor

Abstract

Biological samples can be grouped into separate clusters based on their gene expression profiles. This approach has yielded meaningful biological insights and facilitated biomarker discoveries. Recently, we developed another approach to study connections between biological samples based on their fusion RNA expression. We have used this approach to provide insights into the cell of origin for a mysterious tumor, alveolar rhabdomyosarcoma.

The discovery of AVIL as a bona fide oncogene in glioblastoma

“…In the previous study, we discovered AVIL forming a gene fusion with a housekeeping gene, Methionyl-TRNA Synthetase (MARS), in a pediatric tumor, rhabdomyosarcoma. [4][5][6] Suspecting that other cancers may dysregulate AVIL using different mechanisms, we found that AVIL gene locus is amplified in 15%-18% of glioblastoma cases in The Cancer Genome Atlas (TCGA) studies. 7 However, at protein level, we observed AVIL overexpressed in all of the GBMs we tested.…”

Rhabdomyosarcomas are oncogene addicted to the activation of AVIL

“…AVIL encodes the protein advillin, which is a member of the gelsolin/villin family of actin regulatory proteins ( 7 ). Previously, we identified a gene fusion that joins AVIL with a housekeeping gene MARS (methionyl-tRNA synthetase) in ARMS ( 8 , 9 ). Given that many gene fusions often activate one of the parental genes as a protooncogene and produce oncogenic fusion protein, we hypothesized that the MARS-AVIL fusion and, more importantly, AVIL gene itself might play oncogenic roles in RMS tumorigenesis.…”