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Cited by 854Bone Tumor Diagnosis and TreatmentsSarcoma Diagnosis and TreatmentChromatin Remodeling and Cancer

Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone

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Behjati, Sam, Tarpey, Patrick S, Presneau, Nadège, Scheipl, Susanne, Pillay, Nischalan, Van Loo, Peter, Wedge, David C, Cooke, Susanna L +21 more·2013·Nature Genetics
DOI 10.1038/ng.2814PMC PMC3839851
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Abstract

It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions.

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Authors
Behjati, S., Tarpey, P. S., Presneau, N., Scheipl, S., Pillay, N., Van Loo, P., Wedge, D. C., Cooke, S. L., Gundem, G., Davies, H., Nik-Zainal, S., Martin, S., McLaren, S., Goody, V., Robinson, B., Butler, A., Teague, J. W., Halai, D., Khatri, B., Myklebost, O., Baumhoer, D., Jundt, G., Hamoudi, R., Tirabosco, R., Amary, M. F., Futreal, P. A., Stratton, M. R., Campbell, P. J., & Flanagan, A. M.
Affiliations
  • University of Cambridge (GB)
  • Wellcome Sanger Institute (GB)
  • University College London (GB)
  • Medical University of Graz (AT)
  • Royal National Orthopaedic Hospital NHS Trust (GB)
  • National Health Service (GB)
  • Oslo University Hospital (NO)
  • University Hospital of Basel (CH)
Corresponding author
Flanagan, Adrienne M
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2013-10-27
Volume
45
Issue
12
Pages
1479-1482
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.2814
PMC
PMC3839851
OpenAlex
W2056155872
Cited by
854
References
2
Citations by year
2026: 38 · 2025: 60 · 2024: 72 · 2023: 90 · 2022: 77 · 2021: 101 · 2020: 84 · 2019: 54 · 2018: 64 · 2017: 78 · 2016: 56 · 2015: 38 · 2014: 38 · 2013: 3
FWCI
36.82
Type
journal article
Language
en
Update notices
erratum (2014-02-26)
Open access
Licence
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • WestminsterResearch (University of Westminster) (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lirias (KU Leuven) (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
  • Wellcome Trust (077012/Z/05/Z, 088340, WT088340MA, 098051)
  • Cancer Research UK
  • Rosetrees Trust (M23-F1)
Topics
  • Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
H3F3A, H3F3B, histone H3.3, chondroblastoma, giant cell tumor of bone, driver mutations, stromal cells, osteoclasts, bone tumors
MeSH terms
Amino Acid Sequence, Bone Neoplasms, Cells, Cultured, Child, Chondroblastoma, Gene Frequency, Histones, Humans, Mutation, Case-Control Studies, Giant Cell Tumor of Bone

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