1. Recurrent rearrangements of FOS and FOSB define osteoblastoma.
- Author
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Fittall MW, Mifsud W, Pillay N, Ye H, Strobl AC, Verfaillie A, Demeulemeester J, Zhang L, Berisha F, Tarabichi M, Young MD, Miranda E, Tarpey PS, Tirabosco R, Amary F, Grigoriadis AE, Stratton MR, Van Loo P, Antonescu CR, Campbell PJ, Flanagan AM, and Behjati S
- Subjects
- Adolescent, Adult, Amino Acid Sequence, Animals, Base Sequence, Bone Neoplasms diagnosis, Bone Neoplasms metabolism, Child, Child, Preschool, Female, Gene Rearrangement, Humans, Male, Mice, Middle Aged, Mutation, Osteoblastoma diagnosis, Osteoblastoma metabolism, Proto-Oncogene Proteins c-fos metabolism, Whole Genome Sequencing methods, Young Adult, Bone Neoplasms genetics, Osteoblastoma genetics, Proto-Oncogene Proteins c-fos genetics
- Abstract
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.
- Published
- 2018
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