Genomic architecture characterizes tumor progression paths and fate in breast cancer patients.
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.
Russnes
Hege G
HG
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.
Vollan
Hans Kristian Moen
HKM
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.
Lingjærde
Ole Christian
OC
Biomedical Research Group, Department of Informatics, University of Oslo, P.O. Box 1080 Blindern, 0316 Oslo, Norway.
Krasnitz
Alexander
A
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Lundin
Pär
P
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, SE-171 76 Stockholm, Sweden.
Naume
Bjørn
B
Department of Oncology, Division of Surgery and Cancer, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Sørlie
Therese
T
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Borgen
Elin
E
Division of Pathology, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Rye
Inga H
IH
Division of Pathology, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Langerød
Anita
A
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Chin
Suet-Feung
SF
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.
Teschendorff
Andrew E
AE
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.
Stephens
Philip J
PJ
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Månér
Susanne
S
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, SE-171 76 Stockholm, Sweden.
Schlichting
Ellen
E
Department of Breast and Endocrine Surgery, Division of Surgery and Cancer, Oslo University Hospital, 0450 Oslo, Norway.
Baumbusch
Lars O
LO
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.
Kåresen
Rolf
R
Department of Breast and Endocrine Surgery, Division of Surgery and Cancer, Oslo University Hospital, 0450 Oslo, Norway.
Stratton
Michael P
MP
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.
Wigler
Michael
M
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Caldas
Carlos
C
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.
Zetterberg
Anders
A
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, SE-171 76 Stockholm, Sweden.
Hicks
James
J
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Børresen-Dale
Anne-Lise
AL
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.|Insitute for Clinical Medicine, Faculty of Medicine, University of Oslo.
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