Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer
Robert Lesurf, Miriam Ragle Aure, Hanne Håberg Mørk, Valeria Vitelli, Oslo Breast Cancer Research Consortium (OSBREAC), Steinar Lundgren, Anne-Lise Børresen-Dale, Vessela Kristensen, Fredrik Wärnberg, Michael Hallett, Therese Sørlie, Torill Sauer, Jürgen Geisler, Solveig Hofvind, Elin Borgen, Anne-Lise Børresen-Dale, Olav Engebråten, Øystein Fodstad, Øystein Garred, Gry Aarum Geitvik, Rolf Kåresen, Bjørn Naume, Gunhild Mari Mælandsmo, Hege G Russnes, Ellen Schlichting, Therese Sørlie, Ole Christian Lingjærde, Vessela Kristensen, Kristine Kleivi Sahlberg, Helle Kristine Skjerven, Britt Fritzman, Robert Lesurf, Miriam Ragle Aure, Hanne Håberg Mørk, Valeria Vitelli, Oslo Breast Cancer Research Consortium (OSBREAC), Steinar Lundgren, Anne-Lise Børresen-Dale, Vessela Kristensen, Fredrik Wärnberg, Michael Hallett, Therese Sørlie, Torill Sauer, Jürgen Geisler, Solveig Hofvind, Elin Borgen, Anne-Lise Børresen-Dale, Olav Engebråten, Øystein Fodstad, Øystein Garred, Gry Aarum Geitvik, Rolf Kåresen, Bjørn Naume, Gunhild Mari Mælandsmo, Hege G Russnes, Ellen Schlichting, Therese Sørlie, Ole Christian Lingjærde, Vessela Kristensen, Kristine Kleivi Sahlberg, Helle Kristine Skjerven, Britt Fritzman
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.
Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Source: PubMed