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Topics {✒️}

bacterial artificial chromosome high-grade estrogen receptor estrogen receptor status oligo-array-based high-resolution analysis article number r215 inter-tumor genomic heterogeneity high-resolution genomic profiles article download pdf array-comparative genomic hybridization tnf-α-nf-κβ high-resolution oligo-array comprehensive genomic profile high-grade er-negative tumors high-grade er-/basal subgroup li ka-shing centre bac-based array cgh evaluate genome-wide correlations oligo-based array cgh van de vijver high-density oligo array putatively low-gii subgroup acgh data preprocessing genome-wide frequency plot predicted low-gii subgroup low-gii subgroup relative copy-number state differences recurrent high-level amplification related subjects cancer research uk mode-normalized log-ratios high-resolution acgh computational biology solutions lymph node negative carlos caldas performed cox regressions lymph node status full access van de wiel genome-wide integration full size image identified low-gii subgroup low-gii subgroup identified natl cancer inst privacy choices/manage cookies coordinate aberrant expression primary breast cancers predicted low-gii subclass 26-sample low-gii subgroup high genomic instability gene-expression profiles

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WebPage:
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         headline:High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer
         description:The characterization of copy number alteration patterns in breast cancer requires high-resolution genome-wide profiling of a large panel of tumor specimens. To date, most genome-wide array comparative genomic hybridization studies have used tumor panels of relatively large tumor size and high Nottingham Prognostic Index (NPI) that are not as representative of breast cancer demographics. We performed an oligo-array-based high-resolution analysis of copy number alterations in 171 primary breast tumors of relatively small size and low NPI, which was therefore more representative of breast cancer demographics. Hierarchical clustering over the common regions of alteration identified a novel subtype of high-grade estrogen receptor (ER)-negative breast cancer, characterized by a low genomic instability index. We were able to validate the existence of this genomic subtype in one external breast cancer cohort. Using matched array expression data we also identified the genomic regions showing the strongest coordinate expression changes ('hotspots'). We show that several of these hotspots are located in the phosphatome, kinome and chromatinome, and harbor members of the 122-breast cancer CAN-list. Furthermore, we identify frequently amplified hotspots on 8q22.3 (EDD1, WDSOF1), 8q24.11-13 (THRAP6, DCC1, SQLE, SPG8) and 11q14.1 (NDUFC2, ALG8, USP35) associated with significantly worse prognosis. Amplification of any of these regions identified 37 samples with significantly worse overall survival (hazard ratio (HR) = 2.3 (1.3-1.4) p = 0.003) and time to distant metastasis (HR = 2.6 (1.4-5.1) p = 0.004) independently of NPI. We present strong evidence for the existence of a novel subtype of high-grade ER-negative tumors that is characterized by a low genomic instability index. We also provide a genome-wide list of common copy number alteration regions in breast cancer that show strong coordinate aberrant expression, and further identify novel frequently amplified regions that correlate with poor prognosis. Many of the genes associated with these regions represent likely novel oncogenes or tumor suppressors.
         datePublished:2007-10-07T00:00:00Z
         dateModified:2007-10-07T00:00:00Z
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            Estrogen Receptor
            Bacterial Artificial Chromosome
            Additional Data File
            Bacterial Artificial Chromosome Clone
            Estrogen Receptor Status
            Animal Genetics and Genomics
            Human Genetics
            Plant Genetics and Genomics
            Microbial Genetics and Genomics
            Bioinformatics
            Evolutionary Biology
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                        name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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ScholarlyArticle:
      headline:High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer
      description:The characterization of copy number alteration patterns in breast cancer requires high-resolution genome-wide profiling of a large panel of tumor specimens. To date, most genome-wide array comparative genomic hybridization studies have used tumor panels of relatively large tumor size and high Nottingham Prognostic Index (NPI) that are not as representative of breast cancer demographics. We performed an oligo-array-based high-resolution analysis of copy number alterations in 171 primary breast tumors of relatively small size and low NPI, which was therefore more representative of breast cancer demographics. Hierarchical clustering over the common regions of alteration identified a novel subtype of high-grade estrogen receptor (ER)-negative breast cancer, characterized by a low genomic instability index. We were able to validate the existence of this genomic subtype in one external breast cancer cohort. Using matched array expression data we also identified the genomic regions showing the strongest coordinate expression changes ('hotspots'). We show that several of these hotspots are located in the phosphatome, kinome and chromatinome, and harbor members of the 122-breast cancer CAN-list. Furthermore, we identify frequently amplified hotspots on 8q22.3 (EDD1, WDSOF1), 8q24.11-13 (THRAP6, DCC1, SQLE, SPG8) and 11q14.1 (NDUFC2, ALG8, USP35) associated with significantly worse prognosis. Amplification of any of these regions identified 37 samples with significantly worse overall survival (hazard ratio (HR) = 2.3 (1.3-1.4) p = 0.003) and time to distant metastasis (HR = 2.6 (1.4-5.1) p = 0.004) independently of NPI. We present strong evidence for the existence of a novel subtype of high-grade ER-negative tumors that is characterized by a low genomic instability index. We also provide a genome-wide list of common copy number alteration regions in breast cancer that show strong coordinate aberrant expression, and further identify novel frequently amplified regions that correlate with poor prognosis. Many of the genes associated with these regions represent likely novel oncogenes or tumor suppressors.
      datePublished:2007-10-07T00:00:00Z
      dateModified:2007-10-07T00:00:00Z
      pageStart:1
      pageEnd:17
      license:http://creativecommons.org/licenses/by/2.0/
      sameAs:https://doi.org/10.1186/gb-2007-8-10-r215
      keywords:
         Estrogen Receptor
         Bacterial Artificial Chromosome
         Additional Data File
         Bacterial Artificial Chromosome Clone
         Estrogen Receptor Status
         Animal Genetics and Genomics
         Human Genetics
         Plant Genetics and Genomics
         Microbial Genetics and Genomics
         Bioinformatics
         Evolutionary Biology
      image:
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      isPartOf:
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         issn:
            1474-760X
         volumeNumber:8
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         name:BioMed Central
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Suet F Chin
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Andrew E Teschendorff
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
                     type:PostalAddress
                  type:Organization
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:John C Marioni
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
                     type:PostalAddress
                  type:Organization
                  name:University of Cambridge, Centre for Mathematical Sciences
                  address:
                     name:Computational Biology Group, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Cambridge, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Yanzhong Wang
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
                     type:PostalAddress
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            name:Nuno L Barbosa-Morais
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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            name:Natalie P Thorne
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                  address:
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            name:Jose L Costa
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                  name:VU University Medical Center
                  address:
                     name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Sarah E Pinder
            affiliation:
                  name:Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
                  address:
                     name:Cambridge Breast Unit, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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            name:Mark A van de Wiel
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                  address:
                     name:Department of Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
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                  name:Vrije Universiteit
                  address:
                     name:Department of Mathematics, Vrije Universiteit, Amsterdam, Netherlands
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            type:Person
            name:Andrew R Green
            affiliation:
                  name:Nottingham City Hospital NHS Trust and University of Nottingham
                  address:
                     name:Histopathology, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Ian O Ellis
            affiliation:
                  name:Nottingham City Hospital NHS Trust and University of Nottingham
                  address:
                     name:Histopathology, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Peggy L Porter
            affiliation:
                  name:Fred Hutchinson Cancer Research Center
                  address:
                     name:Division of Human Biology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Simon Tavaré
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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                     type:PostalAddress
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            type:Person
            name:James D Brenton
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Functional Genomics of Drug Resistance, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Bauke Ylstra
            affiliation:
                  name:VU University Medical Center
                  address:
                     name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Carlos Caldas
            affiliation:
                  name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
                  address:
                     name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
                     type:PostalAddress
                  type:Organization
                  name:Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
                  address:
                     name:Cambridge Breast Unit, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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            email:[email protected]
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      name:Genome Biology
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      name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
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         name:Computational Biology Group, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Cambridge, UK
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      address:
         name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
         type:PostalAddress
      name:University of Cambridge, Centre for Mathematical Sciences
      address:
         name:Computational Biology Group, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Cambridge, UK
         type:PostalAddress
      name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
      address:
         name:Functional Genomics of Drug Resistance, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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      address:
         name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
         type:PostalAddress
      name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
      address:
         name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
         type:PostalAddress
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            address:
               name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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            name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
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            name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
            address:
               name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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            name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
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               name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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            name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
            address:
               name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
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            address:
               name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
               type:PostalAddress
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            address:
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            address:
               name:Cambridge Breast Unit, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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      name:Mark A van de Wiel
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            address:
               name:Department of Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
               type:PostalAddress
            type:Organization
            name:Vrije Universiteit
            address:
               name:Department of Mathematics, Vrije Universiteit, Amsterdam, Netherlands
               type:PostalAddress
            type:Organization
      name:Andrew R Green
      affiliation:
            name:Nottingham City Hospital NHS Trust and University of Nottingham
            address:
               name:Histopathology, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, UK
               type:PostalAddress
            type:Organization
      name:Ian O Ellis
      affiliation:
            name:Nottingham City Hospital NHS Trust and University of Nottingham
            address:
               name:Histopathology, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, UK
               type:PostalAddress
            type:Organization
      name:Peggy L Porter
      affiliation:
            name:Fred Hutchinson Cancer Research Center
            address:
               name:Division of Human Biology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA
               type:PostalAddress
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            address:
               name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
               type:PostalAddress
            type:Organization
            name:University of Cambridge, Centre for Mathematical Sciences
            address:
               name:Computational Biology Group, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Cambridge, UK
               type:PostalAddress
            type:Organization
      name:James D Brenton
      affiliation:
            name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
            address:
               name:Functional Genomics of Drug Resistance, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
               type:PostalAddress
            type:Organization
      name:Bauke Ylstra
      affiliation:
            name:VU University Medical Center
            address:
               name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:Carlos Caldas
      affiliation:
            name:Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre
            address:
               name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
               type:PostalAddress
            type:Organization
            name:Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
            address:
               name:Cambridge Breast Unit, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Computational Biology Group, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Cambridge, UK
      name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Computational Biology Group, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Cambridge, UK
      name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
      name:Cambridge Breast Unit, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
      name:Department of Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
      name:Department of Mathematics, Vrije Universiteit, Amsterdam, Netherlands
      name:Histopathology, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, UK
      name:Histopathology, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, UK
      name:Division of Human Biology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA
      name:Computational Biology Group, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Computational Biology Group, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Cambridge, UK
      name:Functional Genomics of Drug Resistance, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
      name:Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology University of Cambridge, Li Ka-Shing Centre, Cambridge, UK
      name:Cambridge Breast Unit, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

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