Oncotarget

Research Papers:

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

Thomas Fleischer, Jovana Klajic, Miriam Ragle Aure, Riku Louhimo, Arne V. Pladsen, Lars Ottestad, Nizar Touleimat, Marko Laakso, Ann Rita Halvorsen, Grethe I. Grenaker Alnæs, Margit L.H. Riis, Åslaug Helland, Sampsa Hautaniemi, Per Eystein Lønning, Bjørn Naume, Anne-Lise Børresen-Dale, Jörg Tost and Vessela N. Kristensen _

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Oncotarget. 2017; 8:1074-1082. https://doi.org/10.18632/oncotarget.13718

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Abstract

Thomas Fleischer1,*, Jovana Klajic1,2,*, Miriam Ragle Aure1, Riku Louhimo3, Arne V. Pladsen1, Lars Ottestad1, Nizar Touleimat4, Marko Laakso3, Ann Rita Halvorsen1, Grethe I. Grenaker Alnæs1, Margit L.H. Riis2,5,6, Åslaug Helland1,7, Sampsa Hautaniemi3, Per Eystein Lønning8,9, Bjørn Naume10, Anne-Lise Børresen-Dale1, Jörg Tost4, Vessela N. Kristensen1,2

1Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway

2Department of Clinical Molecular Biology and Laboratory Science (EpiGen), Akershus University hospital, Division of Medicine, Lørenskog, Norway

3Systems Biology Laboratory, Institute of Biomedicine and Genome-Scale Biology Research Program, University of Helsinki, Finland

4Laboratory for Epigenetics and Environment, Centre National de Génotypage, CEA – Institut de Génomique, France

5Department of Surgery, Akershus University Hospital, Lørenskog, Norway

6Deptartment of Breast and Endocrine Surgery, Oslo University Hospital, Ullevål, Norway

7Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway

8Section of Oncology, Institute of Clinical Science, University of Bergen, Bergen, Norway

9Department of Oncology, Haukeland University Hospital, Bergen, Norway

10Cancer Clinic, Oslo University Hospital Radiumhospitalet, Oslo, Norway

*These authors contributed equally to this work

Correspondence to:

Vessela N. Kristensen, email: [email protected]

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.


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