title: Characterisation of amplification patterns and target genes at chromosome 11q13 in CCND1-amplified sporadic and familial breast tumours.
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.
authors: Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden. karolina.holm@med.lu.se
authors: Karolina
authors: K
authors: Holm
authors: Johan
authors: J
authors: Staaf
authors: Göran
authors: G
authors: Jönsson
authors: Johan
authors: J
authors: Vallon-Christersson
authors: Haukur
authors: H
authors: Gunnarsson
authors: Adalgeir
authors: A
authors: Arason
authors: Linda
authors: L
authors: Magnusson
authors: Rosa B
authors: RB
authors: Barkardottir
authors: Cecilia
authors: C
authors: Hegardt
authors: Markus
authors: M
authors: Ringnér
authors: Ake
authors: A
authors: Borg
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D019938:Cyclin D1 / Q000235:genetics*; D056915:DNA Copy Number Variations; D005190:Family; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D016019:Survival Analysis
chemical_list: C480344:EMSY protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D019938:Cyclin D1