title: Detection of c-KIT and PDGFRA gene mutations in gastrointestinal stromal tumors: comparison of DHPLC and DNA sequencing methods using a single population-based cohort.
abstract: Mutational analysis of c-KIT or PDGFRA has become an important laboratory assay for patients with gastrointestinal stromal tumors (GISTs) because the results are useful in predicting the responsiveness to imatinib. To assess the diagnostic usefulness of denaturing high-pressure liquid chromatography (DHPLC) in this setting, we performed DHPLC and DNA sequencing to study exons 9, 11, 13, and 17 of c-KIT and exons 12 and 18 of PDGFRA in 54 consecutive cases of GIST collected from a single population. Most (40/54 [74%]) carried c-KIT mutations, and 7 (13%) carried PDGFRA mutations. These results were similar to those described in the literature. It is important to note that DHPLC was found to be highly sensitive, detecting all of the mutations in these 6 exons that were identified by DNA sequencing. Our data suggest that DHPLC is a cost-effective, rapid, and sensitive test for screening for mutations of c-KIT and PDGFRA in GISTs.
authors.affiliation: Department of Laboratory Medicine, Cross Cancer Institute and University of Alberta, Edmonton, Canada.
authors.forename: Angeline
authors.initials: A
authors.lastname: Battochio
authors.forename: Shamayel
authors.initials: S
authors.lastname: Mohammed
authors.forename: Debra
authors.initials: D
authors.lastname: Winthrop
authors.forename: Shilo
authors.initials: S
authors.lastname: Lefresne
authors.forename: Karen
authors.initials: K
authors.lastname: Mulder
authors.forename: Quincy
authors.initials: Q
authors.lastname: Chu
authors.forename: Carolyn
authors.initials: C
authors.lastname: O'Hara
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000191:economics / Q000379:methods*; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009691:Nucleic Acid Denaturation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha