Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer
- PMID: 22610119
- PMCID: PMC3673022
- DOI: 10.1038/ng.2279
Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer
Abstract
Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year. Overtreatment of indolent disease also results in significant morbidity. Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androgen receptor gene) and fusion of ETS family transcription factor genes with androgen-responsive promoters. Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer.
Figures
Comment in
-
Traversing the genomic landscape of prostate cancer from diagnosis to death.Nat Genet. 2012 May 29;44(6):613-4. doi: 10.1038/ng.2301. Nat Genet. 2012. PMID: 22641202
-
Urological cancer: Genetic landscape studies of prostate cancer offer new clues.Nat Rev Clin Oncol. 2012 May 29;9(7):367. doi: 10.1038/nrclinonc.2012.94. Nat Rev Clin Oncol. 2012. PMID: 22641363 No abstract available.
-
Prostate cancer: Painting the genetic landscape of prostate cancer.Nat Rev Urol. 2012 Jun 12;9(7):352. doi: 10.1038/nrurol.2012.118. Nat Rev Urol. 2012. PMID: 22688960 No abstract available.
-
Prostate cancer. Mutational consequences.Nat Rev Cancer. 2012 Jun 14;12(7):450-1. doi: 10.1038/nrc3303. Nat Rev Cancer. 2012. PMID: 22695394
-
A picture with more details is painted for prostate cancer.Asian J Androl. 2012 Nov;14(6):799-800. doi: 10.1038/aja.2012.73. Epub 2012 Jul 30. Asian J Androl. 2012. PMID: 22842705 Free PMC article. No abstract available.
-
Mapping mutations in prostate cancer exomes.Asian J Androl. 2012 Nov;14(6):801-2. doi: 10.1038/aja.2012.75. Epub 2012 Jul 30. Asian J Androl. 2012. PMID: 22842706 Free PMC article.
Similar articles
-
SPOP and FOXA1 mutations are associated with PSA recurrence in ERG wt tumors, and SPOP downregulation with ERG-rearranged prostate cancer.Prostate. 2019 Jul;79(10):1156-1165. doi: 10.1002/pros.23830. Epub 2019 May 15. Prostate. 2019. PMID: 31090082
-
The mutational landscape of lethal castration-resistant prostate cancer.Nature. 2012 Jul 12;487(7406):239-43. doi: 10.1038/nature11125. Nature. 2012. PMID: 22722839 Free PMC article.
-
Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer.Nature. 2019 Jul;571(7765):413-418. doi: 10.1038/s41586-019-1347-4. Epub 2019 Jun 26. Nature. 2019. PMID: 31243372 Free PMC article.
-
The Genomics of Prostate Cancer: emerging understanding with technologic advances.Mod Pathol. 2018 Jan;31(S1):S1-11. doi: 10.1038/modpathol.2017.166. Mod Pathol. 2018. PMID: 29297493 Review.
-
Pioneer of prostate cancer: past, present and the future of FOXA1.Protein Cell. 2021 Jan;12(1):29-38. doi: 10.1007/s13238-020-00786-8. Epub 2020 Sep 18. Protein Cell. 2021. PMID: 32946061 Free PMC article. Review.
Cited by
-
ProstaMine: a bioinformatics tool for identifying subtype-specific co-alterations associated with aggressiveness in prostate cancer.Front Pharmacol. 2024 May 1;15:1360352. doi: 10.3389/fphar.2024.1360352. eCollection 2024. Front Pharmacol. 2024. PMID: 38751776 Free PMC article.
-
PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.J Exp Clin Cancer Res. 2024 May 15;43(1):144. doi: 10.1186/s13046-024-03064-1. J Exp Clin Cancer Res. 2024. PMID: 38745318 Free PMC article.
-
Establishment of primary prostate epithelial and tumorigenic cell lines using a non-viral immortalization approach.Biol Res. 2024 May 4;57(1):21. doi: 10.1186/s40659-024-00507-z. Biol Res. 2024. PMID: 38704600 Free PMC article.
-
ELK3 destabilization by speckle-type POZ protein suppresses prostate cancer progression and docetaxel resistance.Cell Death Dis. 2024 Apr 17;15(4):274. doi: 10.1038/s41419-024-06647-0. Cell Death Dis. 2024. PMID: 38632244 Free PMC article.
-
Analysis of the Gene Networks and Pathways Correlated with Tissue Differentiation in Prostate Cancer.Int J Mol Sci. 2024 Mar 24;25(7):3626. doi: 10.3390/ijms25073626. Int J Mol Sci. 2024. PMID: 38612439 Free PMC article.
References
-
- Jemal A, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. - PubMed
-
- Daskivich TJ, et al. Overtreatment of men with low-risk prostate cancer and significant comorbidity. Cancer. 2011;117:2058–2066. - PubMed
-
- He WW, et al. A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer. Genomics. 1997;43:69–77. - PubMed
-
- Li J, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–1947. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials