Identification of an MLL4‐GPS2 fusion as an oncogenic driver of undifferentiated spindle cell sarcoma in a child

Undifferentiated spindle cell sarcoma (UDS) is a poorly defined or understood entity, essentially a waste‐basket for cases failing to fulfill criteria for better‐established diagnoses based on combined histology, immunohistochemistry, and tumor genetic assays. We identified a novel chromosomal translocation t(17;19)(p13;q13) in a pediatric UDS and have characterized this alteration to show rearrangement of the MLL4 and GPS2 genes, resulting in an in‐frame fusion gene MLL4‐GPS2 , the expression of which promotes anchorage‐independent growth. MLL4 was previously reported to be similarly rearranged in hepatocellular carcinomas, notably those positive for hepatitis B virus. Isolated reports of individual rearrangements of GPS2 in a prostate carcinoma cell line and in glioblastoma multiforme, each with different partner genes, recently emerged from high‐throughput sequencing studies but have not been further evaluated for biological effect. © 2014 Wiley Periodicals, Inc.