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FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes
Open accessAbstract
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. Mutations in the transcription factor FOXA1 that are common in prostate cancer result in gain-of-function effects that promote changes in the differentiation of tumour cells.
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Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723
Integrative Clinical Genomics of Advanced Prostate Cancer
Robinson, D., Van Allen, E. M., Wu, Y.-M., Schultz, N., Lonigro, R. J., Mosquera, J.-M., Montgomery, B., Taplin, M.-E., Pritchard, C. C., Attard, G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.001 · Cited by 3,645
Self-citationThe mutational landscape of lethal castration-resistant prostate cancer
Grasso, C. S., Wu, Y.-M., Robinson, D. R., Cao, X., Dhanasekaran, S. M., Khan, A. P., Quist, M. J., Jing, X., Lonigro, R. J., Brenner, J. C., et al. (2012) · Nature · doi:10.1038/nature11125 · Cited by 2,517
Watson, P. A., Chen, Y. F., Balbas, M. D., Wongvipat, J., Socci, N. D., Viale, A., Kim, K., & Sawyers, C. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012443107 · Cited by 639
The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis
Pomerantz, M. M., Li, F., Takeda, D. Y., Lenci, R., Chonkar, A., Chabot, M., Cejas, P., Vazquez, F., Cook, J., Shivdasani, R. A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3419 · Cited by 470
Controlled gene expression in primary Lgr5 organoid cultures
Koo, B.-K., Stange, D. E., Sato, T., Karthaus, W., Farin, H. F., Huch, M., van Es, J. H., & Clevers, H. (2012) · Nature Methods · doi:10.1038/nmeth.1802 · Cited by 320
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Cited by
Ganesh, K., & Massagué, J. (2021) · Nature Medicine · doi:10.1038/s41591-020-01195-4 · Cited by 1,051
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Balsalobre, A., & Drouin, J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00464-z · Cited by 251
FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer
Han, M., Li, F., Zhang, Y., Dai, P., He, J., Li, Y., Zhu, Y., Zheng, J., Huang, H., Bai, F., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.10.011 · Cited by 166
Arruabarrena-Aristorena, A., Maag, J. L. V., Kittane, S., Cai, Y., Karthaus, W. R., Ladewig, E., Park, J., Kannan, S., Ferrando, L., Cocco, E., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.003 · Cited by 130
Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors
Richters, A., Doyle, S. K., Freeman, D. B., Lee, C., Leifer, B. S., Jagannathan, S., Kabinger, F., Koren, J. V., Struntz, N. B., Urgiles, J., et al. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2020.10.001 · Cited by 86
Metadata
- Authors
- Adams, E. J., Karthaus, W. R., Hoover, E., Liu, D., Gruet, A., Zhang, Z., Cho, H., DiLoreto, R., Chhangawala, S., Liu, Y., Watson, P. A., Davicioni, E., Sboner, A., Barbieri, C. E., Bose, R., Leslie, C. S., & Sawyers, C. L.
- Venue
- Nature
- Published
- 2019-06-26
- Volume
- 571
- Issue
- 7765
- Pages
- 408-412
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2955039931
- Cited by
- 269
- References
- 8
- FWCI
- 18.94
- Type
- journal article
- Language
- en
- Open access
- green
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- Adams, E. J., Karthaus, W. R., Hoover, E., Liu, D., Gruet, A., Zhang, Z., Cho, H., DiLoreto, R., Chhangawala, S., Liu, Y., Watson, P. A., Davicioni, E., Sboner, A., Barbieri, C. E., Bose, R., Leslie, C. S., & Sawyers, C. L. (2019). FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature. https://doi.org/10.1038/s41586-019-1318-9
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