Drivers underpinning the malignant transformation of giant cell tumour of bone
The rare benign giant cell tumour of bone (GCTB) is defined by an almost unique mutation in the H3.3 family of histone genes H3-3A or H3-3B; however, the same mutation is occasionally found in primary malignant bone tumours which share many features with the benign variant. Moreover, lung metastases...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
December 2020
|
| In: |
The journal of pathology
Year: 2020, Jahrgang: 252, Heft: 4, Pages: 433-440 |
| ISSN: | 1096-9896 |
| DOI: | 10.1002/path.5537 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/path.5537 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/path.5537 
|
| Verfasserangaben: | Matthew W Fittall, Iben Lyskjær, Peter Ellery, Patrick Lombard, Jannat Ijaz, Anna-Christina Strobl, Dahmane Oukrif, Maxime Tarabichi, Martin Sill, Christian Koelsche, Gunhild Mechtersheimer, Jonas Demeulemeester, Roberto Tirabosco, Fernanda Amary, Peter J Campbell, Stefan M Pfister, David TW Jones, Nischalan Pillay, Peter Van Loo, Sam Behjati and Adrienne M Flanagan |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1919443886 | ||
| 003 | DE-627 | ||
| 005 | 20250717000143.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250310s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/path.5537 |2 doi | |
| 035 | |a (DE-627)1919443886 | ||
| 035 | |a (DE-599)KXP1919443886 | ||
| 035 | |a (OCoLC)1528020142 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Fittall, Matthew W. |e VerfasserIn |0 (DE-588)1359376224 |0 (DE-627)1919443274 |4 aut | |
| 245 | 1 | 0 | |a Drivers underpinning the malignant transformation of giant cell tumour of bone |c Matthew W Fittall, Iben Lyskjær, Peter Ellery, Patrick Lombard, Jannat Ijaz, Anna-Christina Strobl, Dahmane Oukrif, Maxime Tarabichi, Martin Sill, Christian Koelsche, Gunhild Mechtersheimer, Jonas Demeulemeester, Roberto Tirabosco, Fernanda Amary, Peter J Campbell, Stefan M Pfister, David TW Jones, Nischalan Pillay, Peter Van Loo, Sam Behjati and Adrienne M Flanagan |
| 264 | 1 | |c December 2020 | |
| 300 | |b Illustrationen | ||
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online publiziert: 6. Oktober 2020 in Wiley Online Library | ||
| 500 | |a Gesehen am 10.03.2025 | ||
| 520 | |a The rare benign giant cell tumour of bone (GCTB) is defined by an almost unique mutation in the H3.3 family of histone genes H3-3A or H3-3B; however, the same mutation is occasionally found in primary malignant bone tumours which share many features with the benign variant. Moreover, lung metastases can occur despite the absence of malignant histological features in either the primary or metastatic lesions. Herein we investigated the genetic events of 17 GCTBs including benign and malignant variants and the methylation profiles of 122 bone tumour samples including GCTBs. Benign GCTBs possessed few somatic alterations and no other known drivers besides the H3.3 mutation, whereas all malignant tumours harboured at least one additional driver mutation and exhibited genomic features resembling osteosarcomas, including high mutational burden, additional driver event(s), and a high degree of aneuploidy. The H3.3 mutation was found to predate the development of aneuploidy. In contrast to osteosarcomas, malignant H3.3-mutated tumours were enriched for a variety of alterations involving TERT, other than amplification, suggesting telomere dysfunction in the transformation of benign to malignant GCTB. DNA sequencing of the benign metastasising GCTB revealed no additional driver alterations; polyclonal seeding in the lung was identified, implying that the metastatic lesions represent an embolic event. Unsupervised clustering of DNA methylation profiles revealed that malignant H3.3-mutated tumours are distinct from their benign counterpart, and other bone tumours. Differential methylation analysis identified CCND1, encoding cyclin D1, as a plausible cancer driver gene in these tumours because hypermethylation of the CCND1 promoter was specific for GCTBs. We report here the genomic and methylation patterns underlying the rare clinical phenomena of benign metastasising and malignant transformation of GCTB and show how the combination of genomic and epigenomic findings could potentially distinguish benign from malignant GCTBs, thereby predicting aggressive behaviour in challenging diagnostic cases. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. | ||
| 650 | 4 | |a bone | |
| 650 | 4 | |a cyclin D1 | |
| 650 | 4 | |a drivers | |
| 650 | 4 | |a epigenetic | |
| 650 | 4 | |a genomics | |
| 650 | 4 | |a giant cell tumour | |
| 650 | 4 | |a histone | |
| 650 | 4 | |a methylation | |
| 650 | 4 | |a osteoblast | |
| 650 | 4 | |a osteoclast | |
| 650 | 4 | |a sarcoma | |
| 650 | 4 | |a transformation | |
| 700 | 1 | |a Lyskjær, Iben |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ellery, Peter |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lombard, Patrick |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ijaz, Jannat |e VerfasserIn |4 aut | |
| 700 | 1 | |a Strobl, Anna-Christina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Oukrif, Dahmane |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tarabichi, Maxime |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sill, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kölsche, Christian |d 1983- |e VerfasserIn |0 (DE-588)1012485080 |0 (DE-627)661827313 |0 (DE-576)345469372 |4 aut | |
| 700 | 1 | |a Mechtersheimer, Gunhild |e VerfasserIn |0 (DE-588)1021953024 |0 (DE-627)715842595 |0 (DE-576)170441598 |4 aut | |
| 700 | 1 | |a Demeulemeester, Jonas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tirabosco, Roberto |e VerfasserIn |4 aut | |
| 700 | 1 | |a Amary, Fernanda |e VerfasserIn |4 aut | |
| 700 | 1 | |a Campbell, Peter J |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pfister, Stefan |d 1974- |e VerfasserIn |0 (DE-588)123850215 |0 (DE-627)706450930 |0 (DE-576)293908400 |4 aut | |
| 700 | 1 | |a Jones, David T. W. |e VerfasserIn |0 (DE-588)1058669672 |0 (DE-627)79739334X |0 (DE-576)414823583 |4 aut | |
| 700 | 1 | |a Pillay, Nischalan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Loo, Peter van |e VerfasserIn |4 aut | |
| 700 | 1 | |a Behjati, Sam |e VerfasserIn |4 aut | |
| 700 | 1 | |a Flanagan, Adrienne M |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of pathology |d Bognor Regis [u.a.] : Wiley, 1892 |g 252(2020), 4 vom: Dez., Seite 433-440 |h Online-Ressource |w (DE-627)269536957 |w (DE-600)1475280-3 |w (DE-576)078590132 |x 1096-9896 |7 nnas |a Drivers underpinning the malignant transformation of giant cell tumour of bone |
| 773 | 1 | 8 | |g volume:252 |g year:2020 |g number:4 |g month:12 |g pages:433-440 |g extent:8 |a Drivers underpinning the malignant transformation of giant cell tumour of bone |
| 856 | 4 | 0 | |u https://doi.org/10.1002/path.5537 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1002/path.5537 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20250310 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 1058669672 |a Jones, David T. W. |m 1058669672:Jones, David T. W. |d 50000 |e 50000PJ1058669672 |k 0/50000/ |p 17 | ||
| 998 | |g 123850215 |a Pfister, Stefan |m 123850215:Pfister, Stefan |d 910000 |d 910500 |e 910000PP123850215 |e 910500PP123850215 |k 0/910000/ |k 1/910000/910500/ |p 16 | ||
| 998 | |g 1021953024 |a Mechtersheimer, Gunhild |m 1021953024:Mechtersheimer, Gunhild |d 910000 |d 912000 |d 50000 |e 910000PM1021953024 |e 912000PM1021953024 |e 50000PM1021953024 |k 0/910000/ |k 1/910000/912000/ |k 0/50000/ |p 11 | ||
| 998 | |g 1012485080 |a Kölsche, Christian |m 1012485080:Kölsche, Christian |d 910000 |d 912000 |d 50000 |e 910000PK1012485080 |e 912000PK1012485080 |e 50000PK1012485080 |k 0/910000/ |k 1/910000/912000/ |k 0/50000/ |p 10 | ||
| 999 | |a KXP-PPN1919443886 |e 4685758668 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title_sort":"Drivers underpinning the malignant transformation of giant cell tumour of bone","title":"Drivers underpinning the malignant transformation of giant cell tumour of bone"}],"note":["Online publiziert: 6. Oktober 2020 in Wiley Online Library","Gesehen am 10.03.2025"],"person":[{"given":"Matthew W.","role":"aut","roleDisplay":"VerfasserIn","display":"Fittall, Matthew W.","family":"Fittall"},{"given":"Iben","role":"aut","roleDisplay":"VerfasserIn","display":"Lyskjær, Iben","family":"Lyskjær"},{"display":"Ellery, Peter","family":"Ellery","given":"Peter","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Lombard","display":"Lombard, Patrick","role":"aut","roleDisplay":"VerfasserIn","given":"Patrick"},{"roleDisplay":"VerfasserIn","role":"aut","given":"Jannat","family":"Ijaz","display":"Ijaz, Jannat"},{"given":"Anna-Christina","role":"aut","roleDisplay":"VerfasserIn","display":"Strobl, Anna-Christina","family":"Strobl"},{"given":"Dahmane","role":"aut","roleDisplay":"VerfasserIn","display":"Oukrif, Dahmane","family":"Oukrif"},{"given":"Maxime","role":"aut","roleDisplay":"VerfasserIn","display":"Tarabichi, Maxime","family":"Tarabichi"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Martin","family":"Sill","display":"Sill, Martin"},{"given":"Christian","role":"aut","roleDisplay":"VerfasserIn","display":"Kölsche, Christian","family":"Kölsche"},{"roleDisplay":"VerfasserIn","role":"aut","given":"Gunhild","family":"Mechtersheimer","display":"Mechtersheimer, Gunhild"},{"given":"Jonas","roleDisplay":"VerfasserIn","role":"aut","display":"Demeulemeester, Jonas","family":"Demeulemeester"},{"family":"Tirabosco","display":"Tirabosco, Roberto","roleDisplay":"VerfasserIn","role":"aut","given":"Roberto"},{"family":"Amary","display":"Amary, Fernanda","role":"aut","roleDisplay":"VerfasserIn","given":"Fernanda"},{"display":"Campbell, Peter J","family":"Campbell","given":"Peter J","role":"aut","roleDisplay":"VerfasserIn"},{"given":"Stefan","roleDisplay":"VerfasserIn","role":"aut","display":"Pfister, Stefan","family":"Pfister"},{"role":"aut","roleDisplay":"VerfasserIn","given":"David T. W.","family":"Jones","display":"Jones, David T. W."},{"role":"aut","roleDisplay":"VerfasserIn","given":"Nischalan","family":"Pillay","display":"Pillay, Nischalan"},{"given":"Peter van","roleDisplay":"VerfasserIn","role":"aut","display":"Loo, Peter van","family":"Loo"},{"roleDisplay":"VerfasserIn","role":"aut","given":"Sam","family":"Behjati","display":"Behjati, Sam"},{"roleDisplay":"VerfasserIn","role":"aut","given":"Adrienne M","family":"Flanagan","display":"Flanagan, Adrienne M"}],"relHost":[{"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"id":{"doi":["10.1002/(ISSN)1096-9896"],"eki":["269536957"],"zdb":["1475280-3"],"issn":["1096-9896"]},"recId":"269536957","origin":[{"dateIssuedDisp":"1892-","publisherPlace":"Bognor Regis [u.a.]","dateIssuedKey":"1892","publisher":"Wiley"}],"disp":"Drivers underpinning the malignant transformation of giant cell tumour of boneThe journal of pathology","type":{"media":"Online-Ressource","bibl":"periodical"},"part":{"pages":"433-440","issue":"4","text":"252(2020), 4 vom: Dez., Seite 433-440","year":"2020","volume":"252","extent":"8"},"pubHistory":["1.1892 -"],"corporate":[{"display":"Pathological Society of Great Britain and Ireland","role":"isb","roleDisplay":"Herausgebendes Organ"}],"title":[{"title_sort":"journal of pathology","subtitle":"an official journal of the Pathological Society of Great Britain and Ireland","title":"The journal of pathology"}],"note":["Gesehen am 28.02.08"]}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"id":{"eki":["1919443886"],"doi":["10.1002/path.5537"]},"physDesc":[{"noteIll":"Illustrationen","extent":"8 S."}],"name":{"displayForm":["Matthew W Fittall, Iben Lyskjær, Peter Ellery, Patrick Lombard, Jannat Ijaz, Anna-Christina Strobl, Dahmane Oukrif, Maxime Tarabichi, Martin Sill, Christian Koelsche, Gunhild Mechtersheimer, Jonas Demeulemeester, Roberto Tirabosco, Fernanda Amary, Peter J Campbell, Stefan M Pfister, David TW Jones, Nischalan Pillay, Peter Van Loo, Sam Behjati and Adrienne M Flanagan"]},"recId":"1919443886","origin":[{"dateIssuedDisp":"December 2020","dateIssuedKey":"2020"}]} | ||
| SRT | |a FITTALLMATDRIVERSUND2020 | ||