title: Imatinib in the management of multiple gastrointestinal stromal tumors associated with a germline KIT K642E mutation.
abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gut and are distinguished by expression of CD117 (c-Kit). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs. In recent years, examples of familial GIST have been reported in which germline mutations of KIT or PDGFRA result in multiple GISTs, skin disorders, and other abnormalities. The most common germline mutations are in KIT exon 11, mutations in exons 8 and 17 have also been described, and there are 2 families with germline PDGFRA mutations. We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal. To our knowledge, this is only the second germline example of this particular mutation. The patient's esophageal tumors were stabilized with imatinib.
authors.affiliation: Beatson Oncology Centre, Glasgow, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Graham
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Robin
authors.initials: R
authors.lastname: Reid
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Davidson
authors.forename: Jeff D
authors.initials: JD
authors.lastname: White
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004379:Duodenal Neoplasms / Q000235:genetics / Q000601:surgery; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005091:Exons / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000235:genetics / Q000601:surgery; D013274:Stomach Neoplasms / Q000235:genetics / Q000601:surgery