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Identification of clinically relevant drivers of breast cancers in intact mammary epithelium is critical for understanding tumorigenesis yet has proven challenging. Here, we show that intra-amniotic lentiviral injection can efficiently transduce progenitor cells of the adult mammary gland and use that as a platform to functionally screen over 500 genetic lesions for functional roles in tumor formation. Targeted progenitors establish long-term clones of both luminal and myoepithelial lineages in adult animals, and via lineage tracing with stable barcodes, we found that each mouse mammary gland is generated from a defined number of ∼120 early progenitor cells that expand uniformly with equal growth potential. We then designed an in vivo screen to test genetic interactions in breast cancer and identified candidates that drove not only tumor formation but also molecular subtypes. Thus, this methodology enables rapid and high-throughput cancer driver discovery in mammary epithelium.
Pubmed ID: 32059806
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System that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsSoftware tool as collection of command line tools for Short-Reads FASTA/FASTQ files preprocessing.
View all literature mentionsSoftware for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsCell line SK-BR-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Progesterone Receptor
View all literature mentionsThis monoclonal targets CD24
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets alpha smooth muscle Actin
View all literature mentionsThis unknown targets Cytokeratin 14
View all literature mentionsThis monoclonal targets PTEN/ Phosphatase And Tensin Homolog Peptide 1
View all literature mentionsThis monoclonal targets E-cadherin
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets HER2/ErbB2 (29D8) Rabbit mAb
View all literature mentionsThis polyclonal targets p53
View all literature mentionsThis monoclonal targets Keratin, type II; cytokeratin 8/18; EndoA
View all literature mentionsThis polyclonal targets Caspase-3
View all literature mentionsThis monoclonal targets CD29
View all literature mentionsThis recombinant monoclonal targets Estrogen Receptor alpha
View all literature mentionsThis polyclonal targets TSC22D1
View all literature mentionsMus musculus with name STOCK Tg(KRT14-cre)1Amc/J from IMSR.
View all literature mentionsMus musculus with name B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J from IMSR.
View all literature mentionsMus musculus with name B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.
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