LobSig is a multigene predictor of outcome in invasive lobular carcinoma

ILC genomic landscape. a Copy number landscape of 303 ILC tumors as demonstrated by frequency of alteration (%, Y-axis) across the genome (chromosomes on X-axis). Red, amplification (Amp); pink, Gain; light blue, Loss; dark blue, homozygous deletion (HD). b GISTIC significant focal alterations. Amplifications in red and deletions in blue, significant false discovery rate (FDR) in green. c Heatmap of frequency of recurrent co-amplifications in ILC tumors. d FISH analysis showing co-amplification (yellow) of FGFR1 (green) and CCND1 (red) in an ILC case identified as having co-amplification of 8p12 and 11q13 by SNP array. Note increased numbers of signals for both genes in individual nuclei; signals also often clustered/joined (arrows) suggesting a complex clustered rearrangement process involving translocation between these gene regions. e shows normal cells diploid for both genes; f shows a tumor cell nucleus with multiple copies of FGFR1 (green) and a chromosome 8 centromere probe (red); g shows two tumor nuclei analyzed for CCND1 (red) and a chromosome 11 centromere probe (green). LCIS present in the same section displayed the same pattern of co-amplification (not shown), while no evidence of gene copy number change was seen in surrounding columnar cell lesions (not shown). h Boxplot of copy number versus mRNA expression z-scores of FISH targets FGFR1 and CCND1; central line is median, with whiskers extending from the 25th and 75th percentiles. I Spearman genes plotted as ρ across chromosomal location (X-axis) and ANOVA genes plotted as ？log？P value across chromosomes. Green lines represent cut-off point of significance (ρ？>？0.06; P？<？0.00001