title: A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney-Stratakis dyad.
abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchyme neoplasms of the gastrointestinal tract. Gain-of-function somatic mutations of the KIT or PDGFRA genes represent the most prevalent molecular alterations in GISTs. In Carney-Stratakis dyad, patients portray germline mutations of the succinate dehydrogenase subunits B (SDHB), C (SDHC) and D (SDHD) and develop multifocal GISTs and multicentric paragangliomas (PGLs). We herein report a novel germline SDHB mutation (c.T282A--Ile44Asn) occurring in a 26 years-old patient diagnosed with a spindle cell intermediate risk GIST that did not present KIT/PDGFRA/BRAF gene mutations. Further analyses revealed loss of the wild-type SDHB allele and complete loss of SDHB expression in the tumor tissue. After genetic screening of other family members, we detected in the patient's mother a SDHB mutation without any clinical/laboratorial evidence of GIST or PGL. Altogether, our findings (germline SDHB mutation with absence of PGL in the index case and of GIST and/or PGL in his mother) raise the possibility that this familiar setting corresponds to an incomplete phenotype of the Carney-Stratakis dyad.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, 4200-465, Porto, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Celestino
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: Alexandra
authors.initials: A
authors.lastname: Faustino
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.forename: António
authors.initials: A
authors.lastname: Gouveia
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001216:Asparagine / Q000235:genetics; D005190:Family; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018095:Germ-Line Mutation; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010236:Paraganglioma, Extra-Adrenal / Q000209:etiology; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D007532:Isoleucine; D001216:Asparagine; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase