title: Mutations in the RET proto-oncogene and the von Hippel-Lindau disease tumour suppressor gene in sporadic and syndromic phaeochromocytomas.
abstract: Phaeochromocytomas may occur sporadically, or as part of the inherited cancer syndromes multiple endocrine neoplasia (MEN) type 2, von Hippel-Lindau disease (VHL), and, rarely, in type 1 neurofibromatosis. In MEN 2, germline missense mutations have been found in one of eight codons within exons 10, 11, 13, 14, and 16 of the RET proto-oncogene. In VHL, germline mutations within one of the three exons are responsible for the majority of cases. To determine if somatic mutations similar to those seen in the germline in MEN 2 or VHL disease play a role in the pathogenesis of sporadic or familial phaeochromocytomas, we analysed 48 sporadic tumours and tumours from 17 MEN 2 and five VHL patients for mutations in RET exons 9, 10, 11, 13, 14, 15, and 16, and the entire coding sequence of VHL. Five of 48 sporadic phaeochromocytomas had RET mutations within exons 10, 11, and 16. Of these, one was proven to be germline and two were proven to be somatic mutations. Four of 48 had VHL mutations; these included both the bilateral cases in the series (one was proven to be a germline mutation) and two others, of which one was proven somatic.
authors.affiliation: CRC Human Cancer Genetics Research Group, University of Cambridge, UK.
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: P A
authors.initials: PA
authors.lastname: Crossey
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: C S
authors.initials: CS
authors.lastname: Healey
authors.forename: C
authors.initials: C
authors.lastname: Houghton
authors.forename: A
authors.initials: A
authors.lastname: Prowse
authors.forename: S L
authors.initials: SL
authors.lastname: Chew
authors.forename: P L
authors.initials: PL
authors.lastname: Dahia
authors.forename: J L
authors.initials: JL
authors.lastname: O'Riordan
authors.forename: S P
authors.initials: SP
authors.lastname: Toledo
mesh_terms: D029721:Drosophila Proteins; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics; D009154:Mutation; D010673:Pheochromocytoma / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila