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Most Ewing's sarcomas harbor chromosomal translocations that encode fusions between EWS and ETS family members. The most common fusion, EWS/FLI, consists of an EWSR1-derived strong transcriptional activation domain fused, in frame, to the DNA binding domain-containing portion of FLI1. EWS/FLI functions as an aberrant transcription factor to regulate genes that mediate the oncogenic phenotype of Ewing's sarcoma. One of these regulated genes, NR0B1, encodes a corepressor protein, and likely plays a transcriptional role in tumorigenesis. However, the genes that NR0B1 regulates and the transcription factors it interacts with in Ewing's sarcoma are largely unknown. We used transcriptional profiling and chromatin immunoprecipitation to identify genes that are regulated by NR0B1, and compared these data to similar data for EWS/FLI. While the transcriptional profile overlapped as expected, we also found that the genome-wide localization of NR0B1and EWS/FLI overlapped as well, suggesting that they regulate some genes coordinately. Further analysis revealed that NR0B1 and EWS/FLI physically interact. This protein-protein interaction is likely to be relevant for Ewing's sarcoma development because mutations in NR0B1 that disrupt the interaction have transcriptional consequences and also abrogate oncogenic transformation. Taken together, these data suggest that EWS/FLI and NR0B1 physically interact, coordinately modulate gene expression, and mediate the transformed phenotype of Ewing's sarcoma.

Motivation Next-generation sequencing technology is transitioning quickly from research labs to clinical settings. The diagnosis and treatment selection for many acquired and autosomal conditions necessitate a method for accurately detecting somatic and germline variants. Results We have developed Pisces, a rapid, versatile and accurate small-variant calling suite designed for somatic and germline amplicon sequencing applications. Accuracy is achieved by four distinct modules, each incorporating a number of novel algorithmic strategies. Availability and implementation Pisces is distributed under an open source license and can be downloaded from https://github.com/Illumina/Pisces . Pisces is available on the BaseSpace™ SequenceHub. It is distributed on Illumina sequencing platforms such as the MiSeq™ and is included in the Praxis™ Extended RAS Panel test which was recently approved by the FDA. Supplementary information Supplementary data are available at Bioinformatics online.