PMID- 28643781
OWN - NLM
STAT- MEDLINE
DCOM- 20190102
LR  - 20240210
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 8
DP  - 2017 Jun 23
TI  - Recurrent mutation of IGF signalling genes and distinct patterns of genomic 
      rearrangement in osteosarcoma.
PG  - 15936
LID - 10.1038/ncomms15936 [doi]
LID - 15936
AB  - Osteosarcoma is a primary malignancy of bone that affects children and adults. 
      Here, we present the largest sequencing study of osteosarcoma to date, comprising 
      112 childhood and adult tumours encompassing all major histological subtypes. A 
      key finding of our study is the identification of mutations in insulin-like 
      growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this 
      observation using fluorescence in situ hybridization (FISH) in an additional 87 
      osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of 
      tumours. These findings may inform patient selection in future trials of IGF1R 
      inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct 
      rearrangement profiles including a process characterized by chromothripsis and 
      amplification. This process operates recurrently at discrete genomic regions and 
      generates driver mutations. It may represent an age-independent mutational 
      mechanism that contributes to the development of osteosarcoma in children and 
      adults alike.
FAU - Behjati, Sam
AU  - Behjati S
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
AD  - Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK.
AD  - Corpus Christi College, Cambridge CB2 1RH, UK.
FAU - Tarpey, Patrick S
AU  - Tarpey PS
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Haase, Kerstin
AU  - Haase K
AUID- ORCID: 0000-0002-0944-5618
AD  - The Francis Crick Institute, London NW1 1AT, UK.
FAU - Ye, Hongtao
AU  - Ye H
AD  - Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, 
      Stanmore, Middlesex HA7 4LP, UK.
FAU - Young, Matthew D
AU  - Young MD
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Alexandrov, Ludmil B
AU  - Alexandrov LB
AUID- ORCID: 0000-0003-3596-4515
AD  - Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los 
      Alamos, New Mexico 87545, USA.
FAU - Farndon, Sarah J
AU  - Farndon SJ
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
AD  - UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
FAU - Collord, Grace
AU  - Collord G
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Wedge, David C
AU  - Wedge DC
AUID- ORCID: 0000-0002-7572-3196
AD  - Oxford Big Data Institute and Oxford Centre for Cancer Gene Research, Wellcome 
      Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
FAU - Martincorena, Inigo
AU  - Martincorena I
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Cooke, Susanna L
AU  - Cooke SL
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Davies, Helen
AU  - Davies H
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Mifsud, William
AU  - Mifsud W
AD  - UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
FAU - Lidgren, Mathias
AU  - Lidgren M
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Martin, Sancha
AU  - Martin S
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Latimer, Calli
AU  - Latimer C
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Maddison, Mark
AU  - Maddison M
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Butler, Adam P
AU  - Butler AP
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Teague, Jon W
AU  - Teague JW
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Pillay, Nischalan
AU  - Pillay N
AD  - Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, 
      Stanmore, Middlesex HA7 4LP, UK.
AD  - University College London Cancer Institute, Huntley Street, London WC1E 6BT, UK.
FAU - Shlien, Adam
AU  - Shlien A
AD  - Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, 
      Toronto, Ontario, Canada M5G 1X8.
FAU - McDermott, Ultan
AU  - McDermott U
AUID- ORCID: 0000-0001-9032-4700
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Futreal, P Andrew
AU  - Futreal PA
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
AD  - Department of Genomic Medicine, MD Anderson Cancer Center, University of Texas, 
      Houston, Texas 77030, USA.
FAU - Baumhoer, Daniel
AU  - Baumhoer D
AD  - Bone Tumour Reference Centre, Institute of Pathology, University Hospital Basel, 
      University of Basel, Basel 4031, Switzerland.
FAU - Zaikova, Olga
AU  - Zaikova O
AD  - Oslo University Hospital, Oslo 0379, Norway.
FAU - Bjerkehagen, Bodil
AU  - Bjerkehagen B
AD  - Oslo University Hospital, Oslo 0379, Norway.
FAU - Myklebost, Ola
AU  - Myklebost O
AUID- ORCID: 0000-0002-2866-3223
AD  - Oslo University Hospital, Oslo 0379, Norway.
AD  - University of Bergen, Bergen 5020, Norway.
FAU - Amary, M Fernanda
AU  - Amary MF
AD  - Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, 
      Stanmore, Middlesex HA7 4LP, UK.
FAU - Tirabosco, Roberto
AU  - Tirabosco R
AD  - Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, 
      Stanmore, Middlesex HA7 4LP, UK.
FAU - Van Loo, Peter
AU  - Van Loo P
AUID- ORCID: 0000-0003-0292-1949
AD  - The Francis Crick Institute, London NW1 1AT, UK.
AD  - Department of Human Genetics, University of Leuven, Leuven B-3000, Belgium.
FAU - Stratton, Michael R
AU  - Stratton MR
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
FAU - Flanagan, Adrienne M
AU  - Flanagan AM
AD  - Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, 
      Stanmore, Middlesex HA7 4LP, UK.
AD  - University College London Cancer Institute, Huntley Street, London WC1E 6BT, UK.
FAU - Campbell, Peter J
AU  - Campbell PJ
AD  - Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome 
      Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
AD  - Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 
      2XY, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 18387/CRUK_/Cancer Research UK/United Kingdom
GR  - 21777/CRUK_/Cancer Research UK/United Kingdom
GR  - MR/N005813/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170623
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (IGF1 protein, human)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
CIN - Nat Rev Endocrinol. 2017 Sep;13(9):506-508. PMID: 28776583
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - *Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Osteosarcoma/*genetics/metabolism
MH  - Receptor, IGF Type 1/genetics/metabolism
MH  - Signal Transduction
MH  - Young Adult
PMC - PMC5490007
COIS- The authors declare no competing financial interests.
EDAT- 2017/06/24 06:00
MHDA- 2019/01/03 06:00
PMCR- 2017/06/23
CRDT- 2017/06/24 06:00
PHST- 2016/10/12 00:00 [received]
PHST- 2017/05/15 00:00 [accepted]
PHST- 2017/06/24 06:00 [entrez]
PHST- 2017/06/24 06:00 [pubmed]
PHST- 2019/01/03 06:00 [medline]
PHST- 2017/06/23 00:00 [pmc-release]
AID - ncomms15936 [pii]
AID - 10.1038/ncomms15936 [doi]
PST - epublish
SO  - Nat Commun. 2017 Jun 23;8:15936. doi: 10.1038/ncomms15936.