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         headline:Characterisation of amplification patterns and target genes at chromosome 11q13 in CCND1-amplified sporadic and familial breast tumours
         description: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.
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      headline:Characterisation of amplification patterns and target genes at chromosome 11q13 in CCND1-amplified sporadic and familial breast tumours
      description: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.
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      name:Markus Ringnér
      affiliation:
            name:Lund University
            address:
               name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
               type:PostalAddress
            type:Organization
            name:Lund University, BMC C13
            address:
               name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
               type:PostalAddress
            type:Organization
      name:Åke Borg
      affiliation:
            name:Lund University
            address:
               name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
               type:PostalAddress
            type:Organization
            name:Lund University, BMC C13
            address:
               name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
               type:PostalAddress
            type:Organization
            name:Lund University
            address:
               name:Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
      name:Department of Pathology, Laboratory of Cell Biology, Landspitali University Hospital, Reykjavik, Iceland
      name:Department of Pathology, Laboratory of Cell Biology, Landspitali University Hospital, Reykjavik, Iceland
      name:Faculty of Medicine, University of Iceland, Reykjavik, Iceland
      name:Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden
      name:Department of Pathology, Laboratory of Cell Biology, Landspitali University Hospital, Reykjavik, Iceland
      name:Faculty of Medicine, University of Iceland, Reykjavik, Iceland
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, BMC C13, Lund, Sweden
      name:Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
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