Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data.

[dedifferentiated liposarcoma]

Cancer gene fusions that encode a chimeric protein are often characterized by an intragenic discontinuity in the RNA \expression levels of the exons that are 5 ' or 3 ' to the fusion point in one or both of the fusion partners due to differences in the levels of activation of their respective promoters . Based on this , we developed an unbiased , genome-wide bioinformatic screen for gene fusions using Affymetrix Exon array expression data . Using a training set of 46 samples with different known gene fusions , we developed a data analysis pipeline , the "Fusion Score (FS ) model ", to score and rank genes for intragenic changes in expression . In a separate discovery set of 41 tumor samples with possible unknown gene fusions , the FS model generated a list of 552 candidate genes . The transcription factor gene NCOA 2 was one of the candidates identified in a mesenchymal chondrosarcoma . A novel HEY 1 -NCOA 2 fusion was identified by 5 ' RACE , representing an in -frame fusion of HEY 1 exon 4 to NCOA 2 exon 13 . RT-PCR or FISH evidence of this HEY 1 -NCOA 2 fusion was present in all additional mesenchymal chondrosarcomas tested with a definitive histologic diagnosis and adequate material for analysis (n = 9 ) but was absent in 15 samples of other subtypes of chondrosarcomas . We also identified a NUP 107 -LGR 5 fusion in a dedifferentiated liposarcoma but analysis of 17 additional samples did not confirm it as a recurrent event in this sarcoma type . The novel HEY 1 -NCOA 2 fusion appears to be the defining and diagnostic gene fusion in mesenchymal chondrosarcomas .

Diseases
Validation

Diseases presenting "known gene fusions, we developed a data" symptom

dedifferentiated liposarcoma

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