The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
PDGFRA Mutations in Gastrointestinal Stromal Tumors: Frequency, Spectrum and In Vitro Sensitivity to Imatinib
Abstract
Purpose: Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT tyrosine kinase, which is a target for the kinase inhibitor imatinib. A subset of GISTs, however, contains mutations in the homologous kinase platelet derived growth factor receptor alpha (PDGFRA), and the most common of these mutations is resistant to imatinib in vitro. Little is known of the other types of PDGFRA mutations that occur in GISTs. Materials and Methods: We determined the KIT and PDGFRA mutation status of 1,105 unique GISTs using a combination of denaturing high-performance liquid chromatography and direct sequencing. Results: There were 80 tumors (7.2%) with a PDGFRA mutation: 66 in exon 18, 11 in exon 12, and three in exon 14. Transient expression of representative PDGFRA isoforms in CHO cells revealed imatinib sensitivity of exon 12 mutations (SPDHE566-571R and insertion ER561-562) and an exon 14 substitution (N659K). However, most isoforms with a substitution involving codon D842 in exon 18 (D842V, RD841-842KI, DI842-843IM) were resistant to the drug, with the exception of D842Y. Interestingly, other mutations in exon 18 (D846Y, N848K, Y849K and HDSN845-848P) were all imatinib sensitive. Proliferation studies with BA/F3 cell lines stably expressing selected PDGFRA mutant isoforms supported these findings. Conclusion: Including our cases, there are 289 reported PDGFRA-mutant GISTs, of which 181 (62.6%) had the imatinib-resistant substitution D842V. However, our findings suggest that more than one third of GISTs with PDGFRA mutations may respond to imatinib and that mutation screening may be helpful in the management of these tumors.
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Cites
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
Demetri, G. D., von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020461 · Cited by 4,389
Self-citationPDGFRA Activating Mutations in Gastrointestinal Stromal Tumors
Heinrich, M. C., Corless, C. L., Duensing, A., McGreevey, L., Chen, C.-J., Joseph, N., Singer, S., Griffith, D. J., Haley, A., Town, A., et al. (2003) · Science · doi:10.1126/science.1079666 · Cited by 2,301
Self-citationKinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C.-J., Van den Abbeele, A. D., Druker, B. J., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.190 · Cited by 2,299
Self-citationCools, J., DeAngelo, D. J., Gotlib, J., Stover, E. H., Legare, R. D., Cortes, J., Kutok, J., Clark, J., Galinsky, I., Griffin, J. D., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa025217 · Cited by 1,718
van Oosterom, A. T., Judson, I., Verweij, J., Stroobants, S., di Paola, E. D., Dimitrijevic, S., Martens, M., Webb, A., Sciot, R., Van Glabbeke, M., et al. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06535-7 · Cited by 1,264
Biology of Gastrointestinal Stromal Tumors
Corless, C. L., Fletcher, J. A., & Heinrich, M. C. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.140 · Cited by 1,224
Self-citationHirota, S., Ohashi, A., Nishida, T., Isozaki, K., Kinoshita, K., Shinomura, Y., & Kitamura, Y. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)01046-1 · Cited by 666
Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review
Miettinen, M., Majidi, M., & Lasota, J. (2002) · European Journal of Cancer · doi:10.1016/s0959-8049(02)80602-5 · Cited by 545
Debiec-Rychter, M., Cools, J., Dumez, H., Sciot, R., Stul, M., Mentens, N., Vranckx, H., Wasag, B., Prenen, H., Roesel, J., et al. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.11.020 · Cited by 494
KIT-Negative Gastrointestinal Stromal Tumors: Proof of Concept and Therapeutic Implications
Medeiros, F., Corless, C. L., Duensing, A., Hornick, J. L., Oliveira, A. M., Heinrich, M. C., Fletcher, J. A., & Fletcher, C. D. M. (2004) · The American Journal of Surgical Pathology · doi:10.1097/00000478-200407000-00007 · Cited by 486
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Cited by
Gastrointestinal stromal tumour
Rubin, B. P., Heinrich, M. C., & Corless, C. L. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60780-6 · Cited by 1,036
Self-citationGastrointestinal stromal tumours: origin and molecular oncology
Corless, C. L., Barnett, C. M., & Heinrich, M. C. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3143 · Cited by 891
Self-citationMolecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors
Heinrich, M. C., Corless, C. L., Blanke, C. D., Demetri, G. D., Joensuu, H., Roberts, P. J., Eisenberg, B. L., von Mehren, M., Fletcher, C. D. M., Sandau, K., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.2265 · Cited by 814
Self-citationDucimetière, F., Lurkin, A., Ranchère-Vince, D., Decouvelaere, A.-V., Péoc'h, M., Istier, L., Chalabreysse, P., Muller, C., Alberti, L., Bringuier, P.-P., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020294 · Cited by 554
Heterogeneity of kinase inhibitor resistance mechanisms in GIST
Liegl, B., Kepten, I., Le, C., Zhu, M., Demetri, G., Heinrich, M., Fletcher, C., Corless, C., & Fletcher, J. (2008) · The Journal of Pathology · doi:10.1002/path.2382 · Cited by 536
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Metadata
- Authors
- Corless, C. L., Schroeder, A., Griffith, D., Town, A., McGreevey, L., Harrell, P., Shiraga, S., Bainbridge, T., Morich, J., & Heinrich, M. C.
- Venue
- Journal of Clinical Oncology
- Published
- 2005-08-10
- Volume
- 23
- Issue
- 23
- Pages
- 5357-5364
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2102769930
- Cited by
- 849
- References
- 33
- FWCI
- 30.59
- Type
- journal article
- Language
- en
- Open access
- closed
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- Corless, C. L., Schroeder, A., Griffith, D., Town, A., McGreevey, L., Harrell, P., Shiraga, S., Bainbridge, T., Morich, J., & Heinrich, M. C. (2005). PDGFRA Mutations in Gastrointestinal Stromal Tumors: Frequency, Spectrum and In Vitro Sensitivity to Imatinib. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2005.14.068
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