Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genomic DNA from 60 cases of acute myeloid leukaemia (AML) was screened for mutations in the c-kit gene. DNA from all 21 exons was subjected to polymerase chain reaction (PCR) amplification and analysis by conformation sensitive gel electrophoresis (CSGE); exons showing altered CSGE patterns were then sequenced. Mutations were identified only in those patients with inv(16) (3/7 cases) or t(8;21) (1/2 cases) and comprised three in-frame deletion plus insertion mutations (exon 8) and one point mutation (exon 10, GTA --> ATA, Val530Ile). Exons 8 and 10 were then analysed in 31 further cases of inv(16) (n = 14) and t(8;21) (n = 17), revealing four additional exon 8 in-frame deletion plus insertion mutations, all of which were in cases of inv(16). All exon 8 in-frame deletion plus insertion mutations (n = 7) involved the loss or replacement of the codon for Asp419 which is highly conserved cross species and is located in the receptor's extracellular domain. The high frequency of the c-kit proto-oncogene exon 8 deletion plus insertion mutations in AML suggests an essential role for this region of the receptor's extracellular domain. The association with inv(16) invites speculation as to the link between these two changes in the pathogenesis of AML.
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PMID:c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. 1055 98

The present study evaluated the expression and mutations of c-kit in peripheral T-cell lymphomas (PTCLs), except for extra-nodal NK/T cell lymphomas, as a potential target for treatment with imatinib mesylate. Fifty-two patients diagnosed with PTCLs (peripheral T-cell lymhoma, unspecified, 38 cases; angioimmunoblastic T-cell, 7 cases; anaplastic large cell, 7 cases) were enrolled. The immunohistochemistry was performed using standard procedures with anti-c-kit monoclonal IgG, while the c-kit mutations were analysed on paraffin-embedded specimens using PCR-single-stranded conformational polymorphism followed by direct DNA sequencing. The median age of the patients was 52 years (19 to approximately 75 years) with a male-to-female ratio of 69%:31%. Weak expression of c-kit was found in 16 (30.8%) patients, while only 3 (5.8%) patients exhibited mutations in exon 11 or exon 13. The c-kit mutations in exon 11 occurred at codon 558 (AAG --> TAG; Lys --> Stop) and at codon 571 (CTA --> ATA; Leu --> Ile), respectively, while the mutation in exon 13 occurred at codon 634 (CGG --> CGA; Arg --> Arg). The current study only found c-kit mutations in a few patients with PTCLs, except for extra-nodal NK/T cell lymphomas. Therefore, c-kit would not seem to be a good target for a new therapeutic approach to PTCLs.
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PMID:c-kit Expression and mutations in peripheral T cell lymphomas, except for extra-nodal NK/T cell lymphomas. 1632 56