Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma.

Nat Commun 2017 06 23;8:15936. Epub 2017 Jun 23.

Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms15936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490007PMC
June 2017
88 Reads

Publication Analysis

Top Keywords

signalling genes
8
igf signalling
8
children adults
8
osteosarcoma
5
recurrently discrete
4
fluorescence situ
4
observation fluorescence
4
discrete genomic
4
validate observation
4
situ hybridization
4
operates recurrently
4
additional osteosarcomas
4
osteosarcomas igf1
4
process operates
4
fish additional
4
hybridization fish
4
cases validate
4
amplification process
4
generates driver
4
insulin-like growth
4

References

(Supplied by CrossRef)

A Luetke et al.
Cancer. Treat. Rev. 2014

JA Perry et al.
Proc. Natl Acad. Sci. USA 2014

X Chen et al.
Cell. Rep. 2014

M Kovac et al.
Nat. Commun. 2015

S Nik-Zainal et al.
Nature 2016

LB Alexandrov et al.
Nature 2013

M Pollak et al.
Best. Pract. Res. Clin. Endocrinol. Metab. 2008

J Wang et al.
Oncotarget 2015

AT De Souza et al.
Nat. Genet. 1995

EA Kolb et al.
Curr. Oncol. Rep. 2009

EA Kolb et al.
Pediatr. Blood Cancer 2010

Similar Publications