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

Marcel Smid; Francisco Rodriguez Gonzalez; Anieta Sieuwerts; R Salgado; Wendy Prager - van der Smissen; Michelle Daane; Anne Galen; S Nik-Zainal; J Staaf; AB Brinkman; MJV de Vijver; AL Richardson; A Fatima; K Berentsen; A Butler; S Martin; HR Davies; Reno Debets; Marion Gelder; Carolien van Deurzen; G MacGrogan; GGGM Van den Eynden; C Purdie; AM Thompson; C Caldas; PN Span; PT Simpson; SR Lakhani; S van Laere; C Desmedt; M Ringner; S Tommasi; J Eyford; A Broeks; A Vincent-Salomon; PA Futreal; S Knappskog; T King; G Thomas; A Viari; A Langerod; AL Borresen-Dale; E Birney; HG Stunnenberg; M Stratton; John Foekens; John Martens

doi:10.1038/ncomms12910

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

Marcel Smid, Francisco Rodriguez Gonzalez, Anieta Sieuwerts, R Salgado, Wendy Prager - van der Smissen, Michelle Daane, Anne Galen, S Nik-Zainal, J Staaf, AB Brinkman, MJV de Vijver, AL Richardson, A Fatima, K Berentsen, A Butler, S Martin, HR Davies, Reno Debets, Marion Gelder, Carolien van DeurzenG MacGrogan, GGGM Van den Eynden, C Purdie, AM Thompson, C Caldas, PN Span, PT Simpson, SR Lakhani, S van Laere, C Desmedt, M Ringner, S Tommasi, J Eyford, A Broeks, A Vincent-Salomon, PA Futreal, S Knappskog, T King, G Thomas, A Viari, A Langerod, AL Borresen-Dale, E Birney, HG Stunnenberg, M Stratton, John Foekens, John Martens

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	Undefined/Unknown
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12910
Publication status	Published - 2016

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Cite this

Smid, M., Rodriguez Gonzalez, F., Sieuwerts, A., Salgado, R., Prager - van der Smissen, W., Daane, M., Galen, A., Nik-Zainal, S., Staaf, J., Brinkman, AB., de Vijver, MJV., Richardson, AL., Fatima, A., Berentsen, K., Butler, A., Martin, S., Davies, HR., Debets, R., Gelder, M., ... Martens, J. (2016). Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration. Nature Communications, 7. https://doi.org/10.1038/ncomms12910

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title = "Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration",

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.",

author = "Marcel Smid and {Rodriguez Gonzalez}, Francisco and Anieta Sieuwerts and R Salgado and {Prager - van der Smissen}, Wendy and Michelle Daane and Anne Galen and S Nik-Zainal and J Staaf and AB Brinkman and {de Vijver}, MJV and AL Richardson and A Fatima and K Berentsen and A Butler and S Martin and HR Davies and Reno Debets and Marion Gelder and {van Deurzen}, Carolien and G MacGrogan and {Van den Eynden}, GGGM and C Purdie and AM Thompson and C Caldas and PN Span and PT Simpson and SR Lakhani and {van Laere}, S and C Desmedt and M Ringner and S Tommasi and J Eyford and A Broeks and A Vincent-Salomon and PA Futreal and S Knappskog and T King and G Thomas and A Viari and A Langerod and AL Borresen-Dale and E Birney and HG Stunnenberg and M Stratton and John Foekens and John Martens",

year = "2016",

doi = "10.1038/ncomms12910",

language = "Undefined/Unknown",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

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Smid, M, Rodriguez Gonzalez, F, Sieuwerts, A, Salgado, R, Prager - van der Smissen, W, Daane, M, Galen, A, Nik-Zainal, S, Staaf, J, Brinkman, AB, de Vijver, MJV, Richardson, AL, Fatima, A, Berentsen, K, Butler, A, Martin, S, Davies, HR, Debets, R, Gelder, M, van Deurzen, C, MacGrogan, G, Van den Eynden, GGGM, Purdie, C, Thompson, AM, Caldas, C, Span, PN, Simpson, PT, Lakhani, SR, van Laere, S, Desmedt, C, Ringner, M, Tommasi, S, Eyford, J, Broeks, A, Vincent-Salomon, A, Futreal, PA, Knappskog, S, King, T, Thomas, G, Viari, A, Langerod, A, Borresen-Dale, AL, Birney, E, Stunnenberg, HG, Stratton, M, Foekens, J & Martens, J 2016, 'Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration', Nature Communications, vol. 7. https://doi.org/10.1038/ncomms12910

TY - JOUR

T1 - Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

AU - Smid, Marcel

AU - Rodriguez Gonzalez, Francisco

AU - Sieuwerts, Anieta

AU - Salgado, R

AU - Prager - van der Smissen, Wendy

AU - Daane, Michelle

AU - Galen, Anne

AU - Nik-Zainal, S

AU - Staaf, J

AU - Brinkman, AB

AU - de Vijver, MJV

AU - Richardson, AL

AU - Fatima, A

AU - Berentsen, K

AU - Butler, A

AU - Martin, S

AU - Davies, HR

AU - Debets, Reno

AU - Gelder, Marion

AU - van Deurzen, Carolien

AU - MacGrogan, G

AU - Van den Eynden, GGGM

AU - Purdie, C

AU - Thompson, AM

AU - Caldas, C

AU - Span, PN

AU - Simpson, PT

AU - Lakhani, SR

AU - van Laere, S

AU - Desmedt, C

AU - Ringner, M

AU - Tommasi, S

AU - Eyford, J

AU - Broeks, A

AU - Vincent-Salomon, A

AU - Futreal, PA

AU - Knappskog, S

AU - King, T

AU - Thomas, G

AU - Viari, A

AU - Langerod, A

AU - Borresen-Dale, AL

AU - Birney, E

AU - Stunnenberg, HG

AU - Stratton, M

AU - Foekens, John

AU - Martens, John

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms12910

DO - 10.1038/ncomms12910

M3 - Article

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

ER -