Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma.
- Saba KH Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- Cornmark L Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- Hofvander J Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- Magnusson L Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- Nilsson J Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- van den Bos H European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
- Spierings DC European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
- Foijer F European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
- Staaf J Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden.
- Brosjö O Department of Orthopedics, Karolinska University Hospital, Stockholm, Sweden.
- Sumathi VP Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital, Birmingham, UK.
- Lam SW Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
- Szuhai K Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
- Bovée JV Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
- Kovac M Bone Tumour Reference Centre at the Institute of Pathology, University Hospital and University of Basel, Basel, Switzerland.
- Baumhoer D Bone Tumour Reference Centre at the Institute of Pathology, University Hospital and University of Basel, Basel, Switzerland.
- Styring E Department of Orthopedics, Lund University, Skåne University Hospital, Lund, Sweden.
- Nord KH Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- 2020-06-17
Published in:
- The journal of pathology. Clinical research. - 2020
English
Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases. These rearrangements modify the terminal exon of the gene and are believed to stabilise both the FOS transcript and the encoded protein, resulting in high expression levels. Here, we applied in-depth genetic analyses to a series of 29 osteoblastomas, including five classified as epithelioid osteoblastoma. We found recurrent homozygous deletions of the NF2 gene in three of the five epithelioid cases and in one conventional osteoblastoma. These events were mutually exclusive from FOS mutations. Structural variations were determined by deep whole genome sequencing and the number of FOS-rearranged cases was less than previously reported (10/23, 43%). One conventional osteoblastoma displayed a novel mechanism of FOS upregulation; bringing the entire FOS gene under the control of the WNT5A enhancer that is itself activated by FOS. Taken together, we show that NF2 loss characterises a subgroup of osteoblastomas, distinct from FOS-rearranged cases. Both NF2 and FOS are involved in regulating bone homeostasis, thereby providing a mechanistic link to the excessive bone growth of osteoblastoma.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1002/cjp2.172
- PMID 32542935
- Persistent URL
- https://sonar.ch/global/documents/93999
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