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Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

Smid, Marcel; Rodríguez-González, F Germán; Sieuwerts, Anieta M; Salgado, Roberto; Prager-Van der Smissen, Wendy J C; Vlugt-Daane, Michelle van der; van Galen, Anne; Nik-Zainal, Serena; Staaf, Johan LU and Brinkman, Arie B, et al. (2016) In Nature Communications 7.
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... (More)

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.

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Nature Communications
volume
7
publisher
Nature Publishing Group
external identifiers
  • scopus:84989233347
  • wos:000385286300003
ISSN
2041-1723
DOI
10.1038/ncomms12910
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English
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yes
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941ca49e-9b75-4f4b-b2af-64aa170d33be
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2016-10-04 10:48:11
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2017-04-23 04:53:45
@article{941ca49e-9b75-4f4b-b2af-64aa170d33be,
  abstract     = {<p>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.</p>},
  articleno    = {12910},
  author       = {Smid, Marcel and Rodríguez-González, F Germán and Sieuwerts, Anieta M and Salgado, Roberto and Prager-Van der Smissen, Wendy J C and Vlugt-Daane, Michelle van der and van Galen, Anne and Nik-Zainal, Serena and Staaf, Johan and Brinkman, Arie B and van de Vijver, Marc J and Richardson, Andrea L and Fatima, Aquila and Berentsen, Kim and Butler, Adam and Martin, Sancha and Davies, Helen R and Debets, Reno and Gelder, Marion E Meijer-Van and van Deurzen, Carolien H M and MacGrogan, Gaëtan and Van den Eynden, Gert G G M and Purdie, Colin and Thompson, Alastair M and Caldas, Carlos and Span, Paul N and Simpson, Peter T and Lakhani, Sunil R and Van Laere, Steven and Desmedt, Christine and Ringnér, Markus and Tommasi, Stefania and Eyford, Jorunn and Broeks, Annegien and Vincent-Salomon, Anne and Futreal, P Andrew and Knappskog, Stian and King, Tari and Thomas, Gilles and Viari, Alain and Langerød, Anita and Børresen-Dale, Anne-Lise and Birney, Ewan and Stunnenberg, Hendrik G and Stratton, Mike and Foekens, John A and Martens, John W M},
  issn         = {2041-1723},
  language     = {eng},
  month        = {09},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration},
  url          = {http://dx.doi.org/10.1038/ncomms12910},
  volume       = {7},
  year         = {2016},
}