DNA methylation signature (SAM40) identifies subgroups of the Luminal A breast cancer samples with distinct survival

// Thomas Fleischer 1, * , Jovana Klajic 1, 2, * , Miriam Ragle Aure 1 , Riku Louhimo 3 , Arne V. Pladsen 1 , Lars Ottestad 1 , Nizar Touleimat 4 , Marko Laakso 3 , Ann Rita Halvorsen 1 , Grethe I. Grenaker Alnaes 1 , Margit L.H. Riis 2, 5, 6 , Aslaug Helland 1, 7 , Sampsa Hautaniemi 3 , Per Eystein Lonning 8, 9 , Bjorn Naume 10 , Anne-Lise Borresen-Dale 1 , Jorg Tost 4 , Vessela N. Kristensen 1, 2 1 Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway 2 Department of Clinical Molecular Biology and Laboratory Science (EpiGen), Akershus University hospital, Division of Medicine, Lorenskog, Norway 3 Systems Biology Laboratory, Institute of Biomedicine and Genome-Scale Biology Research Program, University of Helsinki, Finland 4 Laboratory for Epigenetics and Environment, Centre National de Genotypage, CEA – Institut de Genomique, France 5 Department of Surgery, Akershus University Hospital, Lorenskog, Norway 6 Deptartment of Breast and Endocrine Surgery, Oslo University Hospital, Ulleval, Norway 7 Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway 8 Section of Oncology, Institute of Clinical Science, University of Bergen, Bergen, Norway 9 Department of Oncology, Haukeland University Hospital, Bergen, Norway 10 Cancer Clinic, Oslo University Hospital Radiumhospitalet, Oslo, Norway * These authors contributed equally to this work Correspondence to: Vessela N. Kristensen, email: v.n.kristensen@medisin.uio.no Keywords: breast cancer, Luminal A, DNA methylation, classification, prognosis Received: June 21, 2016 Accepted: November 07, 2016 Published: November 30, 2016 ABSTRACT Breast cancer patients with Luminal A disease generally have a good prognosis, but among this patient group are patients with good prognosis that are currently overtreated with adjuvant chemotherapy, and also patients that have a bad prognosis and should be given more aggressive treatment. There is no available method for subclassification of this patient group. Here we present a DNA methylation signature (SAM40) that segregates Luminal A patients based on prognosis, and identify one good prognosis group and one bad prognosis group. The prognostic impact of SAM40 was validated in four independent patient cohorts. Being able to subdivide the Luminal A patients may give the two-sided benefit of identifying one subgroup that may benefit from a more aggressive treatment than what is given today, and importantly, identifying a subgroup that may benefit from less treatment.