Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Smid, Marcel 
Rodríguez-González, F Germán 
Sieuwerts, Anieta M 
Salgado, Roberto 
Prager-Van der Smissen, Wendy JC 

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.

Description

Keywords

1112 Oncology and Carcinogenesis, 0604 Genetics, Biomedical, Basic Science, Breast Cancer, Cancer, Genetics, Human Genome, Cancer

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

7

Publisher

Springer Science and Business Media LLC
Sponsorship
European Commission (242006)
Cancer Research UK (16942)
Cancer Research UK (9675)