Fig. 1

Schematic of workflow. Significant histological and transcriptional heterogeneity was found in the MMTV-Myc mouse model of human breast cancer. To ascertain the genetic origins of transcriptional differences and integrate these omics data between histological subtypes, we performed short read whole genome sequencing at a depth of 40 × for three tumors of each unique and predominant histological subtype: microacinar, squamous, and EMT like tumors. Somatic single nucleotide variants, copy number alterations, inversions, and translocations were profiled after alignment and processing of genomic data. Genomic somatic variants were integrated with and compared to previously obtained Affymetrix microarray gene expression and pathway analysis by single sample gene set enrichment analysis (ssGSEA). Integration of multi-omic data enables the identification of thematic pathways driving tumorigenesis and putative oncogenic drivers for each histological subtype. Importantly, these thematic pathways identified in the MMTV-Myc mouse model share similarities in human breast cancer, impactful analogous genetic events in humans co-occur with Myc amplification, and these pathways affect human breast cancer patient overall survival significantly (Created with BioRender.com)