The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma
Open accessAbstract
Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here we describe a systematic method, called Genomic Identification of Significant Targets in Cancer (GISTIC), designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving ≈35 significant events, including 16–18 broad events near chromosome-arm size and 16–21 focal events. Approximately half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have properties different from those with overlapping focal EGFR amplification: the broad events act in part through effects on MET and its ligand HGF and correlate with MET dependence in vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome.
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Cites
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Self-citationMolecular determinants of the response of glioblastomas to EGFR kinase inhibitors
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Self-citationCharacterizing the cancer genome in lung adenocarcinoma
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Self-citationOncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants
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Cited by
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
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Self-citationComprehensive molecular profiling of lung adenocarcinoma
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The landscape of somatic copy-number alteration across human cancers
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Metadata
- Authors
- Beroukhim, R., Getz, G., Nghiemphu, L., Barretina, J., Hsueh, T., Linhart, D., Vivanco, I., Lee, J. C., Huang, J. H., Alexander, S., Du, J., Kau, T., Thomas, R. K., Shah, K., Soto, H., Perner, S., Prensner, J., Debiasi, R. M., Demichelis, F., Hatton, C., Rubin, M. A., Garraway, L. A., Nelson, S. F., Liau, L., Mischel, P. S., Cloughesy, T. F., Meyerson, M., Golub, T. A., Lander, E. S., Mellinghoff, I. K., & Sellers, W. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-12-11
- Volume
- 104
- Issue
- 50
- Pages
- 20007-20012
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2122769974
- Cited by
- 1,075
- References
- 7
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Beroukhim, R., Getz, G., Nghiemphu, L., Barretina, J., Hsueh, T., Linhart, D., Vivanco, I., Lee, J. C., Huang, J. H., Alexander, S., Du, J., Kau, T., Thomas, R. K., Shah, K., Soto, H., Perner, S., Prensner, J., Debiasi, R. M., Demichelis, F., . . . Sellers, W. R. (2007). Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0710052104
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