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BMC Cancer
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers

Authors: Henne Holstege, Erik van Beers, Arno Velds, Xiaoling Liu, Simon A Joosse, Sjoerd Klarenbeek, Eva Schut, Ron Kerkhoven, Christiaan N Klijn, Lodewyk FA Wessels, Petra M Nederlof, Jos Jonkers

Published in: BMC Cancer | Issue 1/2010

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Abstract

Background

Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development.

Methods

To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1 Δ/Δ ;p53 Δ/Δ , Brca2 Δ/Δ ;p53 Δ/Δ and p53 Δ/Δ mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers.

Results

Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYC-associated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2 Δ/Δ ;p53 Δ/Δ tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species.

Conclusions

The selection of the oncogenome during mouse and human breast tumor development is markedly different, apart from the MYC gain and RB1-associated loss. These differences should be kept in mind when using mouse models for preclinical studies.
Appendix
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Metadata
Title
Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers
Authors
Henne Holstege
Erik van Beers
Arno Velds
Xiaoling Liu
Simon A Joosse
Sjoerd Klarenbeek
Eva Schut
Ron Kerkhoven
Christiaan N Klijn
Lodewyk FA Wessels
Petra M Nederlof
Jos Jonkers
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-455

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