Coordinated expression of HER2-neighboring genes in the absence of amplification. (A-H) Expression of genes in the core HER2 amplicon (PGAP3, ERBB2, MIEN1, GRB7), representative genes in the broad HER2 amplicon (MED1, CDK12, NR1D1), and TOP2A (more telomeric on 17q), in HER2A tumors (red), non-HER2A tumors without HER2 overexpression (black), and non-HER2A tumors with HER2 overexpression (o/e, log2 nRPKM + 1 ≥ 8.2; green). (A) Seven non-HER2A, o/e breast tumors. (B) Six non-HER2A, o/e gastric tumors. (C) Two non-HER2A, o/e endometrial tumors. (D) Two non-HER2A, o/e cervix tumors. (E) Two non-HER2A, o/e bladder tumors. (F) Two non-HER2A, o/e lung squamous cell carcinoma tumors. (G) One non-HER2A, o/e lung adenocarcinoma tumor. (H) One non-HER2A, o/e ovarian tumor. (I) Relative copy number levels for broad HER2 amplicon genes in 23 non-HER2A o/e tumors. Relative copy number levels exceed 2 (or are borderline at 1.9) in 6 out of 23 tumors. Tumors are colored by cancer, and genes in the broad HER2 amplicon are colored as per Fig. 2a. (J-M) Average log2 ratio of methylated to unmethylated intensity of CpG probes near HER2 and its closest neighbors PGAP3, MIEN1 and GRB7 (in the gene body or maximum 2 kb upstream of the transcription start site) with Kruskal-Wallis test FDR p value below the indicated value for a four-group comparison: HER2A, non-o/e; HER2A, o/e; non-HER2A, non-o/e; non-HER2A, o/e. (J) For breast cancer, included are 27 methylation probes with Kruskal-Wallis FDR p < 1e-15. (K) For gastric cancer, included are 37 methylation probes with p < 1e-5. (L) For cervix cancer, included are 28 methylation probes with p < 0.01. (M) For bladder cancer, included are 21 methylation probes with p < 0.01. (PDF 571 kb
