Recurrent rearrangements of FOS and FOSB define osteoblastomaMore about Open Access at the Crick
Authors listMatthew 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.
Journal Nature Communications
Issue number 1