KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors

Christopher Corless, Laura McGreevey, Ajia Town, Arin Schroeder, Troy Bainbridge, Patina Harrell, Jonathan A. Fletcher, Michael Heinrich

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)366-370
Number of pages5
JournalJournal of Molecular Diagnostics
Volume6
Issue number4
StatePublished - Nov 2004

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Gene Deletion
Introns
Exons
Gastrointestinal Stromal Tumors
Mutation
Neoplasms
RNA Splice Sites
Phosphotransferases
Complementary DNA
Translational Medical Research
DNA Sequence Analysis
Genes
Protein Isoforms
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Corless, C., McGreevey, L., Town, A., Schroeder, A., Bainbridge, T., Harrell, P., ... Heinrich, M. (2004). KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors. Journal of Molecular Diagnostics, 6(4), 366-370.

KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors. / Corless, Christopher; McGreevey, Laura; Town, Ajia; Schroeder, Arin; Bainbridge, Troy; Harrell, Patina; Fletcher, Jonathan A.; Heinrich, Michael.

In: Journal of Molecular Diagnostics, Vol. 6, No. 4, 11.2004, p. 366-370.

Research output: Contribution to journalArticle

Corless, C, McGreevey, L, Town, A, Schroeder, A, Bainbridge, T, Harrell, P, Fletcher, JA & Heinrich, M 2004, 'KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors', Journal of Molecular Diagnostics, vol. 6, no. 4, pp. 366-370.
Corless C, McGreevey L, Town A, Schroeder A, Bainbridge T, Harrell P et al. KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors. Journal of Molecular Diagnostics. 2004 Nov;6(4):366-370.
Corless, Christopher ; McGreevey, Laura ; Town, Ajia ; Schroeder, Arin ; Bainbridge, Troy ; Harrell, Patina ; Fletcher, Jonathan A. ; Heinrich, Michael. / KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors. In: Journal of Molecular Diagnostics. 2004 ; Vol. 6, No. 4. pp. 366-370.
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