Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
Marcel Smid
(1)
,
F. Germán Rodríguez-González
(1)
,
Anieta M. Sieuwerts
(1)
,
Roberto Salgado
(2)
,
Wendy J. C. Prager-van Der Smissen
(1)
,
Michelle van Der Vlugt-Daane
(1)
,
Anne van Galen
(1)
,
Serena Nik-Zainal
(3)
,
Johan Staaf
(4)
,
Arie B. Brinkman
(5)
,
Marc J. van de Vijver
(6)
,
Andrea L. Richardson
(7)
,
Aquila Fatima
(1)
,
Kim Berentsen
(5)
,
Adam Butler
(3)
,
Sancha Martin
(3)
,
Helen R. Davies
(3)
,
Reno Debets
(1)
,
Marion E. Meijer-Van Gelder
(1, 8)
,
Carolien H. M. van Deurzen
(1)
,
Gaëtan Macgrogan
(9)
,
Gert G. G. M. van den Eynden
(10)
,
Colin Purdie
(11)
,
Alastair M. Thompson
(11)
,
Carlos Caldas
(12)
,
Paul N. Span
(13, 14)
,
Peter T. Simpson
(15)
,
Sunil R. Lakhani
(15)
,
Steven van Laere
(16, 17)
,
Christine Desmedt
(2)
,
Markus Ringnér
(4)
,
Stefania Tommasi
(18)
,
Jorunn Eyford
(19)
,
Anne Broeks
(20)
,
Anne Vincent-Salomon
(21, 22)
,
P. Andrew Futreal
(23)
,
Stian Knappskog
(24)
,
Tari A King
(25)
,
Gilles Thomas
(26)
,
Alain Viari
(27, 28)
,
Anita Langerød
(29)
,
Anne-Lise Børresen-Dale
(29)
,
Ewan Birney
(3)
,
Hendrik G. Stunnenberg
(30)
,
Mike Stratton
(3)
,
John A. Foekens
(1)
,
John W. M. Martens
(1)
1
Erasmus MC -
Erasmus University Medical Center [Rotterdam]
2 Breast Cancer Translational Research Laboratory
3 The Wellcome Trust Sanger Institute [Cambridge]
4 Skane University Hospital [Lund]
5 Radboud University [Nijmegen]
6 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
7 Dana-Farber Cancer Institute [Boston]
8 Department of Medical Oncology
9 VINCO - Validation et identification de nouvelles cibles en oncologie
10 Institut Jules Bordet [Bruxelles]
11 Department of Pathology [Dundee]
12 CAM - University of Cambridge [UK]
13 Department of Radiation Oncology 874
14 Department of Laboratory Medicine
15 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
16 Department Medical Oncology
17 Department of Pathology
18 Beckman Research Institute [Duarte, CA]
19 University of Iceland [Reykjavik]
20 NKI - Netherlands Cancer Institute
21 U830 - Unité de génétique et biologie des cancers
22 Department of Tumor Biology
23 MD Anderson Cancer Center [Houston]
24 UiB - University of Bergen
25 Esso UK Ltd, Department of Exploration,
26 Fondation Synergie Lyon Cancer [Lyon]
27 Baobab
28 ERABLE - Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale
29 Oslo University Hospital Radiumhospitalet
30 Department of Molecular Biology [Nijmegen]
2 Breast Cancer Translational Research Laboratory
3 The Wellcome Trust Sanger Institute [Cambridge]
4 Skane University Hospital [Lund]
5 Radboud University [Nijmegen]
6 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
7 Dana-Farber Cancer Institute [Boston]
8 Department of Medical Oncology
9 VINCO - Validation et identification de nouvelles cibles en oncologie
10 Institut Jules Bordet [Bruxelles]
11 Department of Pathology [Dundee]
12 CAM - University of Cambridge [UK]
13 Department of Radiation Oncology 874
14 Department of Laboratory Medicine
15 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
16 Department Medical Oncology
17 Department of Pathology
18 Beckman Research Institute [Duarte, CA]
19 University of Iceland [Reykjavik]
20 NKI - Netherlands Cancer Institute
21 U830 - Unité de génétique et biologie des cancers
22 Department of Tumor Biology
23 MD Anderson Cancer Center [Houston]
24 UiB - University of Bergen
25 Esso UK Ltd, Department of Exploration,
26 Fondation Synergie Lyon Cancer [Lyon]
27 Baobab
28 ERABLE - Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale
29 Oslo University Hospital Radiumhospitalet
30 Department of Molecular Biology [Nijmegen]
Roberto Salgado
- Fonction : Auteur
- PersonId : 779439
- ORCID : 0000-0002-1110-3801
Carlos Caldas
- Fonction : Auteur
- PersonId : 769434
- ORCID : 0000-0003-3547-1489
Steven van Laere
- Fonction : Auteur
- PersonId : 779440
- ORCID : 0000-0003-2465-3252
Christine Desmedt
- Fonction : Auteur
- PersonId : 764697
- ORCID : 0000-0002-5223-5579
Anne Vincent-Salomon
- Fonction : Auteur
- PersonId : 758892
- ORCID : 0000-0001-5754-5771
P. Andrew Futreal
- Fonction : Auteur
- PersonId : 769444
- ORCID : 0000-0001-8663-2671
Alain Viari
- Fonction : Auteur
- PersonId : 18170
- IdHAL : alain-viari
- ORCID : 0000-0002-1329-7777
- IdRef : 081478151
Résumé
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.
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers éditeurs autorisés sur une archive ouverte
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