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The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer

Open access
Kumar, Akash, Coleman, Ilsa, Morrissey, Colm, Zhang, Xiaotun, True, Lawrence D, Gulati, Roman, Etzioni, Ruth, Bolouri, Hamid, Montgomery, Bruce, White, Thomas, Lucas, Jared M, Brown, Lisha G, Dumpit, Ruth F, DeSarkar, Navonil, Higano, Celestia, Yu, Evan Y, Coleman, Roger, Schultz, Nikolaus, Fang, Min, Lange, Paul H, Shendure, Jay, Vessella, Robert L, Nelson, Peter S·2016·Nature Medicine
DOI 10.1038/nm.4053
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Abstract

Tumor heterogeneity may reduce the efficacy of molecularly guided systemic therapy for cancers that have metastasized. To determine whether the genomic alterations in a single metastasis provide a reasonable assessment of the major oncogenic drivers of other dispersed metastases in an individual, we analyzed multiple tumors from men with disseminated prostate cancer through whole-exome sequencing, array comparative genomic hybridization (CGH) and RNA transcript profiling, and we compared the genomic diversity within and between individuals. In contrast to the substantial heterogeneity between men, there was limited diversity among metastases within an individual. The number of somatic mutations, the burden of genomic copy number alterations and aberrations in known oncogenic drivers were all highly concordant, as were metrics of androgen receptor (AR) activity and cell cycle activity. AR activity was inversely associated with cell proliferation, whereas the expression of Fanconi anemia (FA)-complex genes was correlated with elevated cell cycle progression, expression of the E2F transcription factor 1 (E2F1) and loss of retinoblastoma 1 (RB1). Men with somatic aberrations in FA-complex genes or in ATM serine/threonine kinase (ATM) exhibited significantly longer treatment-response durations to carboplatin than did men without defects in genes encoding DNA-repair proteins. Collectively, these data indicate that although exceptions exist, evaluating a single metastasis provides a reasonable assessment of the major oncogenic driver alterations that are present in disseminated tumors within an individual, and thus may be useful for selecting treatments on the basis of predicted molecular vulnerabilities.

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Metadata

Authors
Kumar, A., Coleman, I., Morrissey, C., Zhang, X., True, L. D., Gulati, R., Etzioni, R., Bolouri, H., Montgomery, B., White, T., Lucas, J. M., Brown, L. G., Dumpit, R. F., DeSarkar, N., Higano, C., Yu, E. Y., Coleman, R., Schultz, N., Fang, M., Lange, P. H., Shendure, J., Vessella, R. L., & Nelson, P. S.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2016-02-29
Volume
22
Issue
4
Pages
369-378
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.4053
OpenAlex
W2292362441
Cited by
738
References
11
FWCI
72.03
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer. https://app.cochat.ai/papers/10.1038/nm.4053
The paper
Kumar, A., Coleman, I., Morrissey, C., Zhang, X., True, L. D., Gulati, R., Etzioni, R., Bolouri, H., Montgomery, B., White, T., Lucas, J. M., Brown, L. G., Dumpit, R. F., DeSarkar, N., Higano, C., Yu, E. Y., Coleman, R., Schultz, N., Fang, M., . . . Nelson, P. S. (2016). Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer. Nature Medicine. https://doi.org/10.1038/nm.4053

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.