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Nat Genet. 2013 Dec;45(12):1479-82. doi: 10.1038/ng.2814. Epub 2013 Oct 27.

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

Author information

1
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
2
Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY.
3
University College London Cancer Institute, Huntley Street, London, WC1E 6BT, UK.
4
Sarah Cannon / University College London Advanced Diagnostics Molecular Profiling Research Laboratories, Capper Street, London, WC1E 6JA, UK.
5
Universitätsklinik für Orthopädie und Orthopädische Chirurgie, Medizinische Universität, Graz, Austria.
6
Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, HA7 4LP, UK.
7
Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, Herestraat 49 box 602, B-3000 Leuven, Belgium.
8
Department of Tumour Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
9
Bone Tumour Reference Centre, Institute of Pathology, University Hospital Basel, Basel, Switzerland.
10
Department of Haematology, Addenbrooke's Hospital, Cambridge, UK.
11
Department of Haematology, University of Cambridge, Hills Road, Cambridge, CB2 2XY.
#
Contributed equally

Erratum in

  • Nat Genet. 2014 Mar;46(3):316. Goodie, Victoria [corrected to Goody, Victoria].

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.

PMID:
24162739
PMCID:
PMC3839851
DOI:
10.1038/ng.2814
[Indexed for MEDLINE]
Free PMC Article
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