Conservation of Breast Cancer Molecular Subtypes and Transcriptional Patterns of Tumor Progression Across Distinct Ethnic Populations

Kolmogorov-Smirnov (KS) analysis to determine whether genes exhibiting strong differences in expression between the ER+ and ER− subtypes in our Asian data set also exhibited a similar behavior in the Caucasian data set. The X axis represents the list of genes from the Caucasian data set (10) ordered by their signal to noise ratio (20) according to their ER classification. The running sum (Y axis) of consecutive values of the Vector V (see ref. 18 for details) indicates the distribution of gene expression signatures derived from the Asian-Chinese population within the Caucasian data set, after removal of several well-known ER marker genes (i.e., ESR1, GATA3, TFF1, TFF3, XBP1, MYB, IGFR1, MUC1, BCL2). The statistic S (KS score) is the maximum score of the running sum. The statistical significance of statistic S is indicated by the P-value (see Supplementary Information4 and ref. ,18 for details).

A–D, examples of DCIS samples used in this study. Two samples are shown (A, B), and (C, D). The DCIS status of each sample was confirmed both by examination of paraffin-embedded H&E sections of samples (A and C, HE) and by examination of frozen cryosections (B and D, FS) of the actual sample that was processed for expression profiling. DCIS samples express the hallmark genes of invasive carcinoma subtypes. E, PCA analysis of normal tissue and DCIS tumors on the 367-gene set. Red, normal samples; blue, DCIS samples. The vertical axis, principal component 1; the horizontal axis, principal component 2. F, unsupervised clustering of DCIS and IDC tumors. Lines, DCIS samples. Eight of 17 DCIS samples cluster within the ERBB2+ group, 8 samples in the ER+ group, and 1 sample was in the ER− group. Red, ER+/Luminal-like; pink, ERBB2+; blue, ER−/Basal-like. Colored bars to the right of the clustergram: A, Luminal epithelial genes with ER; B, genes with ERBB2; C, Basal epithelial genes.