Breast Cancer Research and Treatment

, Volume 133, Issue 2, pp 583–594

Characterisation of amplification patterns and target genes at chromosome 11q13 in CCND1-amplified sporadic and familial breast tumours

  • Karolina Holm
  • Johan Staaf
  • Göran Jönsson
  • Johan Vallon-Christersson
  • Haukur Gunnarsson
  • Adalgeir Arason
  • Linda Magnusson
  • Rosa B. Barkardottir
  • Cecilia Hegardt
  • Markus Ringnér
  • Åke Borg
Preclinical study

DOI: 10.1007/s10549-011-1817-3

Cite this article as:
Holm, K., Staaf, J., Jönsson, G. et al. Breast Cancer Res Treat (2012) 133: 583. doi:10.1007/s10549-011-1817-3

Abstract

Amplification of chromosomal region 11q13, containing the cell cycle regulatory gene CCND1, is frequently found in breast cancer and other malignancies. It is associated with the favourable oestrogen receptor (ER)-positive breast tumour phenotype, but also with poor prognosis and treatment failure. 11q13 spans almost 14 Mb and contains more than 200 genes and is affected by various patterns of copy number gains, suggesting complex mechanisms and selective pressure during tumour progression. In this study, we used 32 k tiling BAC array CGH to analyse 94 CCND1-amplified breast tumours from sporadic, hereditary, and familial breast cancers to fine map chromosome 11q13. A set containing 281 CCND1-non-amplified breast tumours was used for comparisons. We used gene expression data to further validate the functional effect of gene amplification. We identified six core regions covering 11q13.1-q14.1 that were amplified in different combinations. The major core contained CCND1, whereas two cores were found proximal of CCND1 and three distal. The majority of the CCND1-amplified tumours were ER-positive and classified as luminal B. Furthermore, we found that CCND1 amplification is associated with a more aggressive phenotype within histological grade 2 tumours and luminal A subtype tumours. Amplification was equally prevalent in familial and sporadic tumours, but strikingly rare in BRCA1- and BRCA2-mutated tumours. We conclude that 11q13 includes many potential target genes in addition to CCND1.

Keywords

CCND111q13Array comparative genomic hybridisationBreast cancerGene amplification

Abbreviations

aCGH

Array comparative genomic hybridisation

BFB

Breakage-fusion-bridge

CCND1+

CCND1-amplified tumours

CCND1

CCND1-non-amplified tumours

ER

Oestrogen receptor

FGA

Fraction of genome altered

FISH

Fluorescence in situ hybridisation

GEO

Gene expression omnibus

GEX

Gene expression

GISTIC

Genomic identification of significant targets in cancer

GOBO

Gene expression-based outcome for breast cancer online

OS

Overall survival

PR

Progesterone receptor

SAT

Sample adaptive threshold

SRO

Smallest region of overlap

Supplementary material

10549_2011_1817_MOESM1_ESM.xls (108 kb)
Supplementary material 1 (XLS 109 kb)
10549_2011_1817_MOESM2_ESM.pdf (549 kb)
Supplementary material 2 (PDF 550 kb)

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Karolina Holm
    • 1
    • 2
  • Johan Staaf
    • 1
    • 2
  • Göran Jönsson
    • 1
    • 2
  • Johan Vallon-Christersson
    • 1
    • 2
  • Haukur Gunnarsson
    • 3
  • Adalgeir Arason
    • 3
    • 4
  • Linda Magnusson
    • 5
  • Rosa B. Barkardottir
    • 3
    • 4
  • Cecilia Hegardt
    • 1
  • Markus Ringnér
    • 1
    • 2
  • Åke Borg
    • 1
    • 2
    • 6
  1. 1.Department of Oncology, Clinical SciencesLund UniversityLundSweden
  2. 2.CREATE Health Strategic Centre for Translational Cancer ResearchLund University, BMC C13LundSweden
  3. 3.Department of Pathology, Laboratory of Cell BiologyLandspitali University HospitalReykjavikIceland
  4. 4.Faculty of MedicineUniversity of IcelandReykjavikIceland
  5. 5.Department of Clinical GeneticsUniversity and Regional Laboratories, Skåne University Hospital, Lund UniversityLundSweden
  6. 6.Lund Strategic Research Center for Stem Cell Biology and Cell TherapyLund UniversityLundSweden