Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration.
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Authors
Smid, Marcel
Rodríguez-González, F Germán
Sieuwerts, Anieta M
Salgado, Roberto
Prager-Van der Smissen, Wendy JC
Vlugt-Daane, Michelle van der
van Galen, Anne
Staaf, Johan
Brinkman, Arie B
van de Vijver, Marc J
Richardson, Andrea L
Fatima, Aquila
Berentsen, Kim
Butler, Adam
Martin, Sancha
Davies, Helen
Debets, Reno
Gelder, Marion E Meijer-Van
van Deurzen, Carolien HM
MacGrogan, Gaëtan
Van den Eynden, Gert GGM
Purdie, Colin
Thompson, Alastair M
Span, Paul N
Simpson, Peter T
Van Laere, Steven
Desmedt, Christine
Ringnér, Markus
Tommasi, Stefania
Eyford, Jorunn
Broeks, Annegien
Vincent-Salomon, Anne
Futreal, P Andrew
Knappskog, Stian
King, Tari
Thomas, Gilles
Viari, Alain
Langerød, Anita
Børresen-Dale, Anne-Lise
Birney, Ewan
Stunnenberg, Hendrik G
Stratton, Mike
Foekens, John A
Martens, John WM
Publication Date
2016-09-26Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
7
Pages
12910
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Smid, M., Rodríguez-González, F. G., Sieuwerts, A. M., Salgado, R., Prager-Van der Smissen, W. J., Vlugt-Daane, M. v. d., van Galen, A., et al. (2016). Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration.. Nat Commun, 7 12910. https://doi.org/10.1038/ncomms12910
Abstract
A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.
Sponsorship
European Commission (242006)
Identifiers
External DOI: https://doi.org/10.1038/ncomms12910
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282958
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