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

  • Marcel Smid
  • F Germán Rodríguez-González
  • Anieta M Sieuwerts
  • Roberto Salgado
  • Wendy J C Prager-Van der Smissen
  • Michelle van der Vlugt-Daane
  • Anne van Galen
  • Serena Nik-Zainal
  • Johan Staaf
  • Arie B Brinkman
  • Marc J van de Vijver
  • Andrea L Richardson
  • Aquila Fatima
  • Kim Berentsen
  • Adam Butler
  • Sancha Martin
  • Helen R Davies
  • Reno Debets
  • Marion E Meijer-Van Gelder
  • Carolien H M van Deurzen
  • Gaëtan MacGrogan
  • Gert G G M Van den Eynden
  • Colin Purdie
  • Alastair M Thompson
  • Carlos Caldas
  • Paul N Span
  • Peter T Simpson
  • Sunil R Lakhani
  • Steven Van Laere
  • Christine Desmedt
  • Markus Ringnér
  • Stefania Tommasi
  • Jorunn Eyford
  • Annegien Broeks
  • Anne Vincent-Salomon
  • P Andrew Futreal
  • Stian Knappskog
  • Tari King
  • Gilles Thomas
  • Alain Viari
  • Anita Langerød
  • Anne-Lise Børresen-Dale
  • Ewan Birney
  • Hendrik G Stunnenberg
  • Mike Stratton
  • John A Foekens
  • John W M Martens
Publishing year: 2016-09-27
Language: English
Publication/Series: Nature Communications
Volume: 7
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.


  • Medical Genetics
  • Cell and Molecular Biology
  • Cancer and Oncology


  • ISSN: 2041-1723
Markus Ringnér
E-mail: markus [dot] ringner [at] biol [dot] lu [dot] se

Research engineer

Molecular Cell Biology


Sölvegatan 35, Lund