The long tail of oncogenic drivers in prostate cancer
By J. Armenia, Stephanie A. M. Wankowicz, David Liu, Jianjiong Gao, R. Kundra, Ed Reznik, W. Chatila, D. Chakravarty, G. Han, Ilsa M Coleman and 31 more. Nature Genetics, 2018
754 citations recorded by the source corpus.
Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway. We find that the incidence of significantly mutated genes (SMGs) follows a long-tail distribution, with many genes mutated in less than 3% of cases. We identify a total of 97 SMGs, including 70 not previously implicated in prostate cancer, such as the ubiquitin ligase CUL3 and the transcription factor SPEN. Finally, comparing primary and metastatic prostate cancer identifies a set of genomic markers that may inform risk stratification. Meta-analysis of exome sequencing data identifies new recurrently mutated driver genes for prostate cancer. Comparison of primary and metastatic tumors further identifies genomic markers for advanced prostate cancer that may inform risk stratification.
Subfields: Cancer Research, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/53de5949f9d6c875f82b02417f67eb15485f97a6
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In Cancer Research
In Pulmonary and Respiratory Medicine
Citations in the corpus
- Genetics and biology of prostate cancer (2018, background): “In primary tumors, these mutations are associated with higher Gleason scores (Grasso et al. 2012; Armenia et al. 2018).”
- Post-Translational Modifications That Drive Prostate Cancer Progression (2021, background): “CUL3 Cullin–RING-based E3 ubiquitin ligase Mutated in a subset of PCa indicating possible driving roles [151]”
- A decade of clinical development of PARP inhibitors in perspective (2019, background): “), up to 20%–25% of all mPrC harbour gene defects in different DDR pathways, which represents a significant enrichment when compared with localized, often indolent, prostate tumours [45].”