Additional file 4 of Integrative genomic and transcriptomic analyses illuminate the ontology of HER2-low breast carcinomas
Creators: name: Berrino, Enrico
name: Annaratone, Laura
name: Bellomo, Sara Erika
name: Ferrero, Giulio
name: Gagliardi, Amedeo
name: Bragoni, Alberto
name: Grassini, Dora
name: Guarrera, Simonetta
name: Parlato, Caterina
name: Casorzo, Laura
name: Panero, Mara
name: Sarotto, Ivana
name: Giordano, Silvia
name: Cereda, Matteo
name: Montemurro, Filippo
name: Ponzone, Riccardo
name: Crosetto, Nicola
name: Naccarati, Alessio
name: Sapino, Anna
name: Marchiò, Caterina
Publisher: name: figshare
Year: 2022
Subjects: subject: Genetics
subject: FOS: Biological sciences

description: Additional file 4: Fig. S1. Mutational signatures of HLBCs. The picture reports the real 96-matrix substitution identified in the whole cohort and in each HER2 class. We estimated the mutational signatures comprising all the variants with a VAF&gt;0.1. Donut and bar plots show the relative representation of the best fitting COSMIC v2 signatures with the substitutions identified in the cohorts. Fig. S2. A. Comparison of Variant Classification (VC) distribution among HLBCs and control cohorts. B. Comparison of Variant Type (VT) distribution among HLBCs and control cohorts. C. Comparison of variant pathogenic levels among HLBCs and control cohorts. Fig. S3. Hematoxylin and Eosin (H&amp;E) and immunohistochemical reaction with antibodies raised against MLH1 for HLBC-1-17 characterized by a high TMB (42.52 mut/Mb), microsatellite instability, lack of MLH1 expression. Fig. S4. Heatmaps of pathway scores for HLBCs. A. Unsupervised clustering of pathways score. Annotation for IHC-based classes does not reveal enriched pathways associated with the IHC subclassification. B-C-D. Heatmaps representing the genes belonging to cytokine and chemokines signaling (B), antigen presentation (C), stromal markers (D). Some cases show peculiar upregulation (or downregulation) in these gene sets, regardless of the IHC class. Fig. S5. NMF basic features for the LAURA Classification. A. Line plot of the cophenetic coefficient determined by the rank summary. Coefficients tending to 1 indicate the most robust clusters. A large decrease in the stability was detected for a cluster with 6 groups. Red circled dots represent the selected grouping strategy, the first being the achievement of at least four groups without superimposable features with the PAM50 subtypes. B. Consensus matrix for the four clusters. Annotation for IHC-Class, IHC-subtype, PAM50-subtype, basic genes for the cluster definition, consensus group and NMF silhouette is provided. C. Heatmap reporting the genes driving the clustering. Fig. S6. Genotypic and phenotypic features of the four clusters composing the LAURA Classification. A. Bar-plot describing the distribution of the PAM50 subtypes within the RNA classes. RNA classes are represented as colored dots. B. Bar-plot representing the tumor grade distribution within the RNA classes. C. Boxplot representing the Ki67 IHC score (continuous scale) within the RNA groups. D. Boxplot representing of TMB score (mut/Mb) within the RNA groups. E. OncoPrint of the 85 patients analyzed for class discovery. RNA-based classes are annotated in the bottom map. F. Dot plot depicting the ER and PgR expression values by IHC (continuous scale) within the RNA groups. Fig. S7. A. Boxplot representing the Adhesion and Migration score within the RNA groups. B. Boxplot representing the stromal markers score within the RNA groups. C. Representative micrographs of: i) a lobular carcinoma of classic type displaying a targetoid growth pattern around a residual duct and discohesiveness of tumor cells (see white spaces between cells), ii-iv) three different low grade carcinomas showing a marker fibro-elastotic stroma (arrows).