title: Genomic architecture characterizes tumor progression paths and fate in breast cancer patients.
abstract: Distinct molecular subtypes of breast carcinomas have been identified, but translation into clinical use has been limited. We have developed two platform-independent algorithms to explore genomic architectural distortion using array comparative genomic hybridization data to measure (i) whole-arm gains and losses [whole-arm aberration index (WAAI)] and (ii) complex rearrangements [complex arm aberration index (CAAI)]. By applying CAAI and WAAI to data from 595 breast cancer patients, we were able to separate the cases into eight subgroups with different distributions of genomic distortion. Within each subgroup data from expression analyses, sequencing and ploidy indicated that progression occurs along separate paths into more complex genotypes. Histological grade had prognostic impact only in the luminal-related groups, whereas the complexity identified by CAAI had an overall independent prognostic power. This study emphasizes the relation among structural genomic alterations, molecular subtype, and clinical behavior and shows that objective score of genomic complexity (CAAI) is an independent prognostic marker in breast cancer.
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.|Division of Pathology, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.|Insitute for Clinical Medicine, Faculty of Medicine, University of Oslo.
authors.forename: Hege G
authors.initials: HG
authors.lastname: Russnes
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.|Insitute for Clinical Medicine, Faculty of Medicine, University of Oslo.|Department of Breast and Endocrine Surgery, Division of Surgery and Cancer, Oslo University Hospital, 0450 Oslo, Norway.
authors.forename: Hans Kristian Moen
authors.initials: HKM
authors.lastname: Vollan
authors.affiliation: Biomedical Research Group, Department of Informatics, University of Oslo, P.O. Box 1080 Blindern, 0316 Oslo, Norway.
authors.forename: Ole Christian
authors.initials: OC
authors.lastname: Lingjærde
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Krasnitz
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, SE-171 76 Stockholm, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Lundin
authors.affiliation: Department of Oncology, Division of Surgery and Cancer, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Sørlie
authors.affiliation: Division of Pathology, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Borgen
authors.affiliation: Division of Pathology, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
authors.forename: Inga H
authors.initials: IH
authors.lastname: Rye
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
authors.affiliation: Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka-Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Suet-Feung
authors.initials: SF
authors.lastname: Chin
authors.affiliation: Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka-Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.|UCL Cancer Institute, University College London, WC1E 6BT, UK.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Teschendorff
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, SE-171 76 Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Månér
authors.affiliation: Department of Breast and Endocrine Surgery, Division of Surgery and Cancer, Oslo University Hospital, 0450 Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Schlichting
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.|Division of Pathology, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.|Biomedical Research Group, Department of Informatics, University of Oslo, P.O. Box 1080 Blindern, 0316 Oslo, Norway.
authors.forename: Lars O
authors.initials: LO
authors.lastname: Baumbusch
authors.affiliation: Department of Breast and Endocrine Surgery, Division of Surgery and Cancer, Oslo University Hospital, 0450 Oslo, Norway.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kåresen
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.|Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Stratton
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
authors.affiliation: Breast Cancer Functional Genomics, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka-Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.|Cambridge Breast Unit, Addenbrookes Hospital and Cambridge NIHR Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK.
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, SE-171 76 Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Zetterberg
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hicks
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.|Insitute for Clinical Medicine, Faculty of Medicine, University of Oslo.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D055028:Comparative Genomic Hybridization; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D011379:Prognosis; D016016:Proportional Hazards Models