Fig. 5
From: Integrated analyses of murine breast cancer models reveal critical parallels with human disease
11D amplicon presence and function is conserved in human breast cancer. TCGA breast cancer copy number dataset analysis revealed co-amplification of HER2 and the COL1A1 locus through a heatmap across chromosome 17 of multiple samples with each row representing an independent patient sample (a-top) with red representing amplification and blue representing deletion. The COL1A1 amplification event occurred independently of HER2 (A-bottom) as identified by probe intensity of aCGH data of a single TCGA breast cancer patient. The COL1A1/CHAD amplification event was disproportionately found in HER2-positive tumors and is present in ~25% of Her2-positive tumors (b). Gene expression of HER2 + samples with and without the 17q21.33 amplification demonstrated a unique gene expression profile as identified by unsupervised hierarchical clustering (c) and significantly worse overall survival within the KMplotter dataset (P < 0.001, log rank test) (d). CRISPRi-mediated knockdown of CHAD and COL1A1 in human cell line BT-474 resulted in defects in wound healing (e, f) (* = P < 0.05, students two-tailed, unpaired t-test, n = 9) and distant metastasis to the lung after orthotopic injections (g, h n = 10, for WT, n = 4 for CHAD KO1, n = 5 for CHAD KO2 n = 12 for Col1a1 KO1, n = 6 for Col1a1 KO2). Scale bars of 10 µm (e), 5 mm (g top), and 20 µm (g bottom) displayed on image for reference. All error bars presented are standard deviation
