This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Corless, C. L. Articles by Heinrich, M. C. Search for Related Content PubMed PubMed Citation Articles by Corless, C. L. Articles by Heinrich, M. C.

JMD 2004, Vol. 6, No. 4
Copyright © 2004 American Society for Investigative Pathology & Association for Molecular Pathology

KIT Gene Deletions at the Intron 10–Exon 11 Boundary in GI Stromal Tumors

Christopher L. Corless^*, Laura McGreevey, Ajia Town, Arin Schroeder, Troy Bainbridge, Patina Harrell, Jonathan A. Fletcher and Michael C. Heinrich

From the Department of Pathology, * Oregon Health & Science University (OHSU) Cancer Institute and the Division of Hematology & Oncology, Oregon Health & Science University, and Portland VA Medical Center, Portland, Oregon; and the Department of Pathology, Brigham & Women’s Hospital, Boston, Massachusetts

Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in the KIT gene, and the majority of these mutations affect the juxtamembrane domain of the kinase encoded by exon 11. Screening GISTs for KIT gene mutations is important for translational research studies and for providing prognostic information on the likelihood of tumor response to treatment with the kinase inhibitor imatinib mesylate (Gleevec). In a series of GISTs analyzed in our laboratory by a combination of denaturing HPLC and direct DNA sequencing, we identified 19 cases with KIT exon 11 deletions that included from 1 to 14 bp of intron 10 sequence and resulted in loss of the normal splice acceptor site at the beginning of exon 11. Predicted use of the next potential splice-acceptor site was confirmed by cDNA sequencing in 4 cases. Thus, the resulting mutant isoform, deletion KPMYEVQWK 550–558, was the same in all 19 cases. Only two other examples of deletions across the intron 10–exon 11 boundary have been reported, yet among 722 GISTs analyzed in our laboratories these deletions were not uncommon, accounting for 3.9% of exon 11 mutations and 2.6% of all tumors. Loss of KIT intron 10 sequences may be under-recognized if the forward primer is too close to exon 11, or if cases are examined exclusively at the cDNA level. Laboratories that offer clinical screening for KIT mutations in GI stromal tumors should be aware of this class of mutations.

This article has been cited by other articles:

				J. Desai, S. Shankar, M. C. Heinrich, J. A. Fletcher, C. D. Fletcher, J. Manola, J. A. Morgan, C. L. Corless, S. George, K. Tuncali, et al. Clonal Evolution of Resistance to Imatinib in Patients with Metastatic Gastrointestinal Stromal Tumors Clin. Cancer Res., September 15, 2007; 13(18): 5398 - 5405. [Abstract] [Full Text] [PDF]

				A. Zamo, A. Bertolaso, I. Franceschetti, G. Weirich, P. Capelli, S. Pecori, M. Chilosi, H. Hoefler, F. Menestrina, and A. Scarpa Microfluidic Deletion/Insertion Analysis for Rapid Screening of KIT and PDGFRA Mutations in CD117-Positive Gastrointestinal Stromal Tumors: Diagnostic Applications and Report of a New KIT Mutation J. Mol. Diagn., April 1, 2007; 9(2): 151 - 157. [Abstract] [Full Text] [PDF]

				M. C. Heinrich, C. L. Corless, C. D. Blanke, G. D. Demetri, H. Joensuu, P. J. Roberts, B. L. Eisenberg, M. von Mehren, C. D.M. Fletcher, K. Sandau, et al. Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors J. Clin. Oncol., October 10, 2006; 24(29): 4764 - 4774. [Abstract] [Full Text] [PDF]

				L Tornillo and L M Terracciano An update on molecular genetics of gastrointestinal stromal tumours. J. Clin. Pathol., June 1, 2006; 59(6): 557 - 563. [Abstract] [Full Text] [PDF]