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Recurrent rearrangements of FOS and FOSB define osteoblastoma

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journal contribution
posted on 15.07.2020 by Matthew W Fittall, William Mifsud, Nischalan Pillay, Hongtao Ye, Anna-Christina Strobl, Annelien Verfaillie, Jonas Demeulemeester, Lei Zhang, Fitim Berisha, Maxime Tarabichi, Matthew D Young, Elena Miranda, Patrick S Tarpey, Roberto Tirabosco, Fernanda Amary, Agamemnon E Grigoriadis, Michael R Stratton, Peter Van Loo, Cristina R Antonescu, Peter J Campbell, Adrienne M Flanagan, Sam Behjati
The transcription factor FOS has long been implicated in the pathogenesis of bone tumours, following the discovery that the viral homologue, v-fos, caused osteosarcoma in laboratory mice. However, mutations of FOS have not been found in human bone-forming tumours. Here, we report recurrent rearrangement of FOS and its paralogue, FOSB, in the most common benign tumours of bone, osteoblastoma and osteoid osteoma. Combining whole-genome DNA and RNA sequences, we find rearrangement of FOS in five tumours and of FOSB in one tumour. Extending our findings into a cohort of 55 cases, using FISH and immunohistochemistry, provide evidence of ubiquitous mutation of FOS or FOSB in osteoblastoma and osteoid osteoma. Overall, our findings reveal a human bone tumour defined by mutations of FOS and FOSB.