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. 2015 Oct;25(10):1521–1535. doi: 10.1101/gr.187823.114

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© 2015 Forsberg et al.; Published by Cold Spring Harbor Laboratory Press

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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Figure 7. — Comprehensive analysis of pathology, gene copy number, and gene expression for case MA018, showing evidence for increased copy number and expression of ERBB2 in normal epithelial as well as in normal mesenchymal cells. (A1) A large-format histology slide of breast tissue stained with hematoxylin and eosin, with diagnosis of multifocal invasive ductal carcinoma (HER2+, non-luminal). Areas of tissue samples taken for DNA extraction, prior to formalin fixation of the tissue, are marked with colored thick lines. Positions of two primary tumors 1 and 2 (PT1 and PT2) are shown in brown. UM1, UM2, and UM3 are labeled in yellow, green, and red, respectively. (np) Normal genetic profiles (see also below, B–G). Two cores from paraffin-embedded breast tissue (thin-lined black circles) surrounding samples UM1 and UM3 were taken for separate analysis using the HER2 tricolor Dual ISH DNA Probe Cocktail Assay (Roche) and the results are shown in A2–A8. Black arrows point to single nuclei of normal mesenchymal stromal cells and epithelial cells containing more than two copies of ERBB2 (black dots). The centromere of Chromosome 17 is stained in red. Note a weak but clearly discernible immunohistochemical staining of HER2 protein in the cell membrane of normal mesenchymal and epithelial cells upon high magnification. (B–G) A segment of Chromosome 17 containing ERBB2 from six samples from Illumina global genome analysis. Skin (SK, normal control tissue) and UM2 samples have normal profiles (np) with no gain of ERBB2. The remaining four samples were scored as containing an increased copy number (red dots) for ERBB2. The total size of aberrations in UM samples is as follows: UM98, 0.7 Mb (not shown in this figure); UM1, 0.9 Mb; UM3, >39% of the genome.