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Gene expression analysis of primary mouse prostate organoid culture with overexpression of FOXA1

UID: 10530

Author(s): Adams, Elizabeth*, Sawyers, Charles L.*, Leslie, Christina* * MSK affiliated

Description
Summary from the GEO: "Gene expression analysis of primary mouse prostate organoid culture with overexpression of FOXA1
Examination by genotypes and days elapsed prepared in 3 replicates."

The study associated with the dataset further explains FOXA1 and how it connects to the dataset:

"Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown1–9. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology. Interrogation of the biological properties of wild-type FOXA1 and fourteen FOXA1 mutants reveals gain of function in mouse prostate organoid proliferation assays. Twelve of these mutants, as well as wild-type FOXA1, promoted an exaggerated pro-luminal differentiation program, whereas two different R219 mutants blocked luminal differentiation and activated a mesenchymal and neuroendocrine transcriptional program. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) of wild-type FOXA1 and representative Wing2 and R219 mutants revealed marked, mutant-specific changes in open chromatin at thousands of genomic loci and exposed sites of FOXA1 binding and associated increases in gene expression. Of note, ATAC-seq peaks in cells expressing R219 mutants lacked the canonical core FOXA1-binding motifs (GTAAAC/T) but were enriched for a related, non-canonical motif (GTAAAG/A), which was preferentially activated by R219-mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its pioneering function and perturb normal luminal epithelial differentiation programs, providing further support for the role of lineage plasticity in cancer progression."
Subject of Study
Mus musculus
Subject(s)
Chromatin
Mutation
Prostatic Neoplasms
OncoTree Cancer Type(s)
Prostate
Access via GEO

Text of RAW sequencing data.
Accession #: GSE128666

Access via SRA

RNA Sequence reads for 36 samples.
Accession #: SRP189075

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA528461

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Adams E, Karthaus W, Hoover E, et al. FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature. 2019; 571(7765):408-412.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Dataset Format(s)
Plain Text, SRA, TAR
Dataset Size
7.1 Mb (TAR of TXT), SRA distributed across 36 files of 1-4 Gb each.
Data Catalog Record Updated
2023-12-07