The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers
Open accessAbstract
To catalog protein-altering mutations that may drive the development of prostate cancers and their progression to metastatic disease systematically, we performed whole-exome sequencing of 23 prostate cancers derived from 16 different lethal metastatic tumors and three high-grade primary carcinomas. All tumors were propagated in mice as xenografts, designated the LuCaP series, to model phenotypic variation, such as responses to cancer-directed therapeutics. Although corresponding normal tissue was not available for most tumors, we were able to take advantage of increasingly deep catalogs of human genetic variation to remove most germline variants. On average, each tumor genome contained ∼200 novel nonsynonymous variants, of which the vast majority was specific to individual carcinomas. A subset of genes was recurrently altered across tumors derived from different individuals, including TP53, DLK2, GPC6, and SDF4. Unexpectedly, three prostate cancer genomes exhibited substantially higher mutation frequencies, with 2,000–4,000 novel coding variants per exome. A comparison of castration-resistant and castration-sensitive pairs of tumor lines derived from the same prostate cancer highlights mutations in the Wnt pathway as potentially contributing to the development of castration resistance. Collectively, our results indicate that point mutations arising in coding regions of advanced prostate cancers are common but, with notable exceptions, very few genes are mutated in a substantial fraction of tumors. We also report a previously undescribed subtype of prostate cancers exhibiting “hypermutated” genomes, with potential implications for resistance to cancer therapeutics. Our results also suggest that increasingly deep catalogs of human germline variation may challenge the necessity of sequencing matched tumor-normal pairs.
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A map of human genome variation from population-scale sequencing.
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An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer
Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., Sun, X.-W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., et al. (2005) · Science · doi:10.1126/science.1117679 · Cited by 3,846
Self-citationTargeted capture and massively parallel sequencing of 12 human exomes
Ng, S. B., Turner, E. H., Robertson, P. D., Flygare, S. D., Bigham, A. W., Lee, C., Shaffer, T., Wong, M., Bhattacharjee, A., Eichler, E. E., et al. (2009) · Nature · doi:10.1038/nature08250 · Cited by 2,030
Self-citationA comprehensive catalogue of somatic mutations from a human cancer genome
Pleasance, E. D., Cheetham, R. K., Stephens, P. J., McBride, D. J., Humphray, S. J., Greenman, C. D., Varela, I., Lin, M.-L., Ordóñez, G. R., Bignell, G. R., et al. (2010) · Nature · doi:10.1038/nature08658 · Cited by 1,696
Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 Gene Fusions in Prostate Cancer
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Cited by
The 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
Organoid Cultures Derived from Patients with Advanced Prostate Cancer
Gao, D., Vela, I., Sboner, A., Iaquinta, P. J., Karthaus, W. R., Gopalan, A., Dowling, C., Wanjala, J. N., Undvall, E. A., Arora, V. K., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.016 · Cited by 1,559
Heitzer, E., Ulz, P., Belic, J., Gutschi, S., Quehenberger, F., Fischereder, K., Benezeder, T., Auer, M., Pischler, C., Mannweiler, S., et al. (2013) · Genome Medicine · doi:10.1186/gm434 · Cited by 357
Hovelson, D. H., McDaniel, A. S., Cani, A. K., Johnson, B., Rhodes, K., Williams, P. D., Bandla, S., Bien, G., Choppa, P., Hyland, F., et al. (2015) · Neoplasia · doi:10.1016/j.neo.2015.03.004 · Cited by 224
Self-citationPoly‐gene fusion transcripts and chromothripsis in prostate cancer
Wu, C., Wyatt, A. W., McPherson, A., Lin, D., McConeghy, B. J., Mo, F., Shukin, R., Lapuk, A. V., M. Jones, S. J., Zhao, Y., et al. (2012) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.21999 · Cited by 51
Metadata
- Authors
- Kumar, A., White, T. A., MacKenzie, A. P., Clegg, N., Lee, C., Dumpit, R. F., Coleman, I., Ng, S. B., Salipante, S. J., Rieder, M. J., Nickerson, D. A., Corey, E., Lange, P. H., Morrissey, C., Vessella, R. L., Nelson, P. S., & Shendure, J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-09-26
- Volume
- 108
- Issue
- 41
- Pages
- 17087-17092
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2009302881
- Cited by
- 263
- References
- 7
- FWCI
- 26.97
- Type
- journal article
- Language
- en
- Open access
- green
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- Kumar, A., White, T. A., MacKenzie, A. P., Clegg, N., Lee, C., Dumpit, R. F., Coleman, I., Ng, S. B., Salipante, S. J., Rieder, M. J., Nickerson, D. A., Corey, E., Lange, P. H., Morrissey, C., Vessella, R. L., Nelson, P. S., & Shendure, J. (2011). Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1108745108
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