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Int. J. Mol. Sci. 2018, 19(1), 196; doi:10.3390/ijms19010196

Dissecting Time- from Tumor-Related Gene Expression Variability in Bilateral Breast Cancer

Department of Applied Research and Technical Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
Department of Medical Oncology, IRCCS Ospedale San Raffaele, 20132 Milano, Italy
Authors to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 29 December 2017 / Accepted: 5 January 2018 / Published: 9 January 2018
(This article belongs to the Special Issue Tumor Microenvironment)
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Metachronous (MBC) and synchronous bilateral breast tumors (SBC) are mostly distinct primaries, whereas paired primaries and their local recurrences (LRC) share a common origin. Intra-pair gene expression variability in MBC, SBC, and LRC derives from time/tumor microenvironment-related and tumor genetic background-related factors and pairs represents an ideal model for trying to dissect tumor-related from microenvironment-related variability. Pairs of tumors derived from women with SBC (n = 18), MBC (n = 11), and LRC (n = 10) undergoing local-regional treatment were profiled for gene expression; similarity between pairs was measured using an intraclass correlation coefficient (ICC) computed for each gene and compared using analysis of variance (ANOVA). When considering biologically unselected genes, the highest correlations were found for primaries and paired LRC, and the lowest for MBC pairs. By instead limiting the analysis to the breast cancer intrinsic genes, correlations between primaries and paired LRC were enhanced, while lower similarities were observed for SBC and MBC. Focusing on stromal-related genes, the ICC values decreased for MBC and were significantly different from SBC. These findings indicate that it is possible to dissect intra-pair gene expression variability into components that are associated with genetic origin or with time and microenvironment by using specific gene subsets. View Full-Text
Keywords: Bilateral breast cancer; local relapses; gene expression profiles; tumor microenvironment; stromal genes; PAM50 Bilateral breast cancer; local relapses; gene expression profiles; tumor microenvironment; stromal genes; PAM50

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Callari, M.; Dugo, M.; Miodini, P.; Veneroni, S.; Bianchini, G.; Daidone, M.G.; Cappelletti, V. Dissecting Time- from Tumor-Related Gene Expression Variability in Bilateral Breast Cancer. Int. J. Mol. Sci. 2018, 19, 196.

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