Recurrent rearrangements of FOS and FOSB define osteoblastomaMore about Open Access at the Crick
Authors listMatthew Fittall Annelien Verfaillie Jonas Demeulemeester Maxime Tarabichi Peter Van Loo William Mifsud Nischalan Pillay Hongtao Ye Anna-Christina Strobl Lei Zhang Fitim Berisha Matthew D Young Elena Miranda Patrick S Tarpey Roberto Tirabosco Fernanda Amary Agamemnon E Grigoriadis Michael R Stratton 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.
Journal Nature Communications
Issue number 1