Publication

Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma

Saba, K. H., Cornmark, L., Hofvander, J., Magnusson, L., Nilsson, J., van den Bos, H., Spierings, D. C., Foijer, F., Staaf, J., Brosjö, O., Sumathi, V. P., Lam, S. W., Szuhai, K., Bovée, J. V., Kovac, M., Baumhoer, D., Styring, E. & Nord, K. H., 16-Jun-2020, In : Journal of pathology clinical research. 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Saba, K. H., Cornmark, L., Hofvander, J., Magnusson, L., Nilsson, J., van den Bos, H., ... Nord, K. H. (2020). Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma. Journal of pathology clinical research. https://doi.org/10.1002/cjp2.172

Author

Saba, Karim H ; Cornmark, Louise ; Hofvander, Jakob ; Magnusson, Linda ; Nilsson, Jenny ; van den Bos, Hilda ; Spierings, Diana Cj ; Foijer, Floris ; Staaf, Johan ; Brosjö, Otte ; Sumathi, Vaiyapuri P ; Lam, Suk Wai ; Szuhai, Karoly ; Bovée, Judith Vmg ; Kovac, Michal ; Baumhoer, Daniel ; Styring, Emelie ; Nord, Karolin H. / Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma. In: Journal of pathology clinical research. 2020.

Harvard

Saba, KH, Cornmark, L, Hofvander, J, Magnusson, L, Nilsson, J, van den Bos, H, Spierings, DC, Foijer, F, Staaf, J, Brosjö, O, Sumathi, VP, Lam, SW, Szuhai, K, Bovée, JV, Kovac, M, Baumhoer, D, Styring, E & Nord, KH 2020, 'Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma', Journal of pathology clinical research. https://doi.org/10.1002/cjp2.172

Standard

Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma. / Saba, Karim H; Cornmark, Louise; Hofvander, Jakob; Magnusson, Linda; Nilsson, Jenny; van den Bos, Hilda; Spierings, Diana Cj; Foijer, Floris; Staaf, Johan; Brosjö, Otte; Sumathi, Vaiyapuri P; Lam, Suk Wai; Szuhai, Karoly; Bovée, Judith Vmg; Kovac, Michal; Baumhoer, Daniel; Styring, Emelie; Nord, Karolin H.

In: Journal of pathology clinical research, 16.06.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Saba KH, Cornmark L, Hofvander J, Magnusson L, Nilsson J, van den Bos H et al. Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma. Journal of pathology clinical research. 2020 Jun 16. https://doi.org/10.1002/cjp2.172


BibTeX

@article{fe90999535464583a807261f81120123,
title = "Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma",
abstract = "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.",
keywords = "FOS, FOSB, NF2, WNT5A, osteoblastoma, osteosarcoma",
author = "Saba, {Karim H} and Louise Cornmark and Jakob Hofvander and Linda Magnusson and Jenny Nilsson and {van den Bos}, Hilda and Spierings, {Diana Cj} and Floris Foijer and Johan Staaf and Otte Brosj{\"o} and Sumathi, {Vaiyapuri P} and Lam, {Suk Wai} and Karoly Szuhai and Bov{\'e}e, {Judith Vmg} and Michal Kovac and Daniel Baumhoer and Emelie Styring and Nord, {Karolin H}",
note = "{\circledC} 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.",
year = "2020",
month = "6",
day = "16",
doi = "10.1002/cjp2.172",
language = "English",
journal = "Journal of pathology clinical research",
issn = "2056-4538",
publisher = "Wiley",

}

RIS

TY - JOUR

T1 - Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma

AU - Saba, Karim H

AU - Cornmark, Louise

AU - Hofvander, Jakob

AU - Magnusson, Linda

AU - Nilsson, Jenny

AU - van den Bos, Hilda

AU - Spierings, Diana Cj

AU - Foijer, Floris

AU - Staaf, Johan

AU - Brosjö, Otte

AU - Sumathi, Vaiyapuri P

AU - Lam, Suk Wai

AU - Szuhai, Karoly

AU - Bovée, Judith Vmg

AU - Kovac, Michal

AU - Baumhoer, Daniel

AU - Styring, Emelie

AU - Nord, Karolin H

N1 - © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.

PY - 2020/6/16

Y1 - 2020/6/16

N2 - 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.

AB - 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.

KW - FOS

KW - FOSB

KW - NF2

KW - WNT5A

KW - osteoblastoma

KW - osteosarcoma

U2 - 10.1002/cjp2.172

DO - 10.1002/cjp2.172

M3 - Article

C2 - 32542935

JO - Journal of pathology clinical research

JF - Journal of pathology clinical research

SN - 2056-4538

ER -

ID: 127902966