biostudies-arrayexpressRobin ShawMus musculusHiSat2, SamtoolsDESeq2bcl2fastqhttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-15078The genes for transcription factor RUNX1 and its binding partner CBFb have been reported to be mutated in human breast cancer. We show for the first time that loss of Runx1 in a genetically engineered mouse model results in accelerated disease onset and tumour development aligning RUNX1 as a tumour suppressor in breast cancer. Combined deletion of Runx1 and the related family member Runx2 resulted in mammary epithelial cells becoming exquisitely sensitive to WNT-driven transformation with the emergence of multiple tumours early in life. Clonogenic assays indicated that Runx1 ablation induced a stem cell like phenotype in mammary epithelial cells whilst transcriptome analysis demonstrated activation of multiple oncogenic pathways, especially when Runx2 was co-deleted. While loss of Runx2 itself did not result in tumour promotion we observed dramatic effects when both Runx2 and Runx1 were deleted. Significantly, altered Runx expression in the mammary epithelium also drove profound alterations in the tumour microenvironment impacting the immune landscape revealing extrinsic effects of Runx gene deletion in mammary tissue. Tissue, mouse model: Cell preparations from 9-week mammary glands were from female mice of the following genotypes: 1) BLG-Cre;Catnbwt/lox(ex3) 2) BLG-Cre;Catnbwt/lox(ex3);Runx1fl/fl 3) BLG-Cre;Catnbwt/lox(ex3);Runx2fl/fl 4) BLG-Cre;Catnbwt/lox(ex3); Runx1fl/fl;Runx2fl/flbiostudies-arrayexpressLibrary Construction - RNA-seq libraries were prepared using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian [Takara Bio]. Following preparation, the quality of the libraries was assessed using the Agilent 2200 TapeStation System with a High Sensitivity D1000 ScreenTape Analysis, and the quantity was measured using a Qubit Fluorometer.Nucleic Acid Extraction - RNA extraction was performed using the RNAqueous™-Micro Total RNA Isolation Kit [Invitrogen], and the protocol provided by the manufacturer was followed. The protocol included a step to remove any residual genomic DNA using the DNA-free™ system.Sequencing - The prepared RNA-seq libraries were sequenced via the Illumina NextSeq 500 System. The sequencing was performed with paired-end (2x36) reads using the MiniSeq High Output Reagent Kit [75-cycles]. Following sequencing, the Illumina sequence data was demultiplexed using bcl2fastq (v2.20)Sample Collection - Mouse mammary glands from 9-week-old female mice of the B-cat+/WT, B-cat+/R1KO, and B-cat+/DKO cohorts.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesData Transformation - Raw counts normalised using R and the bioconducter package DESeq2.Sequence Alignment - RNA-Seq paired-end reads were aligned to the GRCm38.93 version of the mouse genome and annotation and sorted using Samtools.MetabolomicsUnknownTranscriptomicsGenomicsProteomicsD1000 ScreenTape Analysis, Qubit Fluorometer.NextSeq 500RNA-seq of coding RNAMus musculusRobin ShawEwan CameronKirsteen CampbellKaren BlythDimitris AthineosKerri SweeneyAmy LawlorfalseRunx1 and Runx2 act in concert to suppress Wnt/b-catenin-driven mammary tumourigenesis impacting on mammary stemness and the immune microenvironmentThe genes for transcription factor RUNX1 and its binding partner CBFb have been reported to be mutated in human breast cancer. We show for the first time that loss of Runx1 in a genetically engineered mouse model results in accelerated disease onset and tumour development aligning RUNX1 as a tumour suppressor in breast cancer. Combined deletion of Runx1 and the related family member Runx2 resulted in mammary epithelial cells becoming exquisitely sensitive to WNT-driven transformation with the emergence of multiple tumours early in life. Clonogenic assays indicated that Runx1 ablation induced a stem cell like phenotype in mammary epithelial cells whilst transcriptome analysis demonstrated activation of multiple oncogenic pathways, especially when Runx2 was co-deleted. While loss of Runx2 itself did not result in tumour promotion we observed dramatic effects when both Runx2 and Runx1 were deleted. Significantly, altered Runx expression in the mammary epithelium also drove profound alterations in the tumour microenvironment impacting the immune landscape revealing extrinsic effects of Runx gene deletion in mammary tissue. Tissue, mouse model: Cell preparations from 9-week mammary glands were from female mice of the following genotypes: 1) BLG-Cre;Catnbwt/lox(ex3) 2) BLG-Cre;Catnbwt/lox(ex3);Runx1fl/fl 3) BLG-Cre;Catnbwt/lox(ex3);Runx2fl/fl 4) BLG-Cre;Catnbwt/lox(ex3); Runx1fl/fl;Runx2fl/fl2026-05-01T00:00:00Z2026-05-01T01:03:25.554Z2025-04-17T14:03:13.313ZE-MTAB-15078ERP171778EFO_0002944EFO_0004170EFO_0004917EFO_0005518EFO_0003816EFO_0003738EFO_0004184