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Cell Rep. 2016 Jul 26;16(4):1166-1179. doi: 10.1016/j.celrep.2016.06.051. Epub 2016 Jul 7.

Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer.

Author information

1
Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; McGill Centre for Bioinformatics, McGill University, Montreal, QC H3G 1Y6, Canada; Rosalind & Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
2
Institute for Cancer Research and Department of Cancer Genetics, Oslo University Hospital, The Norwegian Radium Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
3
Institute for Cancer Research and Department of Cancer Genetics, Oslo University Hospital, The Norwegian Radium Hospital, 0424 Oslo, Norway.
4
Oslo Center for Biostatistics and Epidemiology and Department of Biostatistics, University of Oslo, 0317 Oslo, Norway.
5
Department of Oncology, St. Olav's University Hospital, 7006 Trondheim, Norway; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
6
Institute for Cancer Research and Department of Cancer Genetics, Oslo University Hospital, The Norwegian Radium Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, 0318 Oslo, Norway; Division of Medicine, Department of Clinical Molecular Biology and Laboratory Science (EpiGen), Akershus University Hospital, 1478 Lørenskog, Norway.
7
Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
8
Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; McGill Centre for Bioinformatics, McGill University, Montreal, QC H3G 1Y6, Canada; School of Computer Science, McGill University, Montreal, QC H3A 0E9, Canada.
9
Institute for Cancer Research and Department of Cancer Genetics, Oslo University Hospital, The Norwegian Radium Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, 0318 Oslo, Norway. Electronic address: therese.sorlie@rr-research.no.

Abstract

Breast cancer consists of at least five main molecular "intrinsic" subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

PMID:
27396337
DOI:
10.1016/j.celrep.2016.06.051
[Indexed for MEDLINE]
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