title: Detection of c-kit exons 11- and 17-activating mutations in testicular seminomas by high-resolution melting amplicon analysis.
abstract: A subgroup of testicular seminomas has been reported to contain activating mutations in KIT, the transmembrane tyrosine kinase receptor encoded by the c-kit gene. Most mutations are in exon 17, although exon 11-activating mutations have recently been described. For patients refractory to standard therapeutic protocols for seminoma, the presence of c-kit-activating mutations in some of these neoplasms might suggest an alternative therapy with KIT targeting drugs. We used the novel mutation scanning technique, high-resolution melting amplicon analysis, to screen a series of 22 testicular seminomas for c-kit-activating mutations. Four cases (18%) had exon 17-activating mutations and these included D816Y, D816V, Y823N and one case that contained both D816E and D820H. A single case (5%) had an exon 11-activating mutation. Interestingly, the exon 11-activating mutation was L576P, the same mutation that characterizes the rare c-kit mutation-positive cases of malignant melanoma. Fluorescence in situ hybridization (FISH) for c-kit suggested that most seminomas are probably polysomic for c-kit and there was not a significant difference in c-kit FISH characteristics between the mutation-positive and mutation-negative cases. The use of high-resolution melting amplicon analysis as a screening technique will allow for the rapid identification of patients with testicular seminomas whose tumors contain c-kit-activating mutations. This could benefit patients whose tumors are refractory to standard therapeutic protocols.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.
authors.forename: Carlynn
authors.initials: C
authors.lastname: Willmore-Payne
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Holden
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Chadwick
authors.forename: Lester J
authors.initials: LJ
authors.lastname: Layfield
mesh_terms: D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D018239:Seminoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044366:Transition Temperature
chemical_list: D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit