The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Somatic ERCC2 Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma
Open accessAbstract
Cisplatin-based chemotherapy is the standard of care for patients with muscle-invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based chemotherapy is associated with improved survival, although molecular determinants of cisplatin response are incompletely understood. We performed whole-exome sequencing on pretreatment tumor and germline DNA from 50 patients with muscle-invasive urothelial carcinoma who received neoadjuvant cisplatin-based chemotherapy followed by cystectomy (25 pT0/pTis “responders,” 25 pT2+ “nonresponders”) to identify somatic mutations that occurred preferentially in responders. ERCC2, a nucleotide excision repair gene, was the only significantly mutated gene enriched in the cisplatin responders compared with nonresponders (q < 0.01). Expression of representative ERCC2 mutants in an ERCC2-deficient cell line failed to rescue cisplatin and UV sensitivity compared with wild-type ERCC2. The lack of normal ERCC2 function may contribute to cisplatin sensitivity in urothelial cancer, and somatic ERCC2 mutation status may inform cisplatin-containing regimen usage in muscle-invasive urothelial carcinoma. Significance: Somatic ERCC2 mutations correlate with complete response to cisplatin-based chemosensitivity in muscle-invasive urothelial carcinoma, and clinically identified mutations lead to cisplatin sensitivity in vitro. Nucleotide excision repair pathway defects may drive exceptional response to conventional chemotherapy. Cancer Discov; 4(10); 1140–53. ©2014 AACR. See related commentary by Turchi et al., p. 1118 This article is highlighted in the In This Issue feature, p. 1103
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“This ERCC2N238S mutation corresponds to one of the recurrent mutational hotspots observed in patients with muscle-invasive urothelial carcinoma who achieved a complete response to neoadjuvant cisplatin-based therapy (21).”
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Metadata
- Authors
- Van Allen, E. M., Mouw, K. W., Kim, P., Iyer, G., Wagle, N., Al-Ahmadie, H., Zhu, C., Ostrovnaya, I., Kryukov, G. V., O'Connor, K. W., Sfakianos, J., Garcia-Grossman, I., Kim, J., Guancial, E. A., Bambury, R., Bahl, S., Gupta, N., Farlow, D., Qu, A., Signoretti, S., Barletta, J. A., Reuter, V., Boehm, J., Lawrence, M., Getz, G., Kantoff, P., Bochner, B. H., Choueiri, T. K., Bajorin, D. F., Solit, D. B., Gabriel, S., D'Andrea, A., Garraway, L. A., & Rosenberg, J. E.
- Venue
- Cancer Discovery
- Published
- 2014-09-30
- Volume
- 4
- Issue
- 10
- Pages
- 1140-1153
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2131178190
- Cited by
- 620
- References
- 5
- FWCI
- 40.92
- Type
- journal article
- Language
- en
- Open access
- green
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- Van Allen, E. M., Mouw, K. W., Kim, P., Iyer, G., Wagle, N., Al-Ahmadie, H., Zhu, C., Ostrovnaya, I., Kryukov, G. V., O'Connor, K. W., Sfakianos, J., Garcia-Grossman, I., Kim, J., Guancial, E. A., Bambury, R., Bahl, S., Gupta, N., Farlow, D., Qu, A., . . . Rosenberg, J. E. (2014). Somatic ERCC2 Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-14-0623
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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.
