title: Genetic aberrance of sporadic MEN 2A component tumours: analysis of RET.
abstract: OBJECTIVE
  The molecular pathogenesis of familial multiple endocrine neoplasia (MEN) type 2 (parathyroid adenoma with medullary thyroid carcinoma and adrenal pheochromocytoma) is associated with a germ-line mutation in the RET proto-oncogene. We undertook this study to clarify the relationship between the tumorigenesis of apparently sporadic MEN type 2 component endocrine tumours and RET mutations.
  
  
  METHODS
  Direct sequencing for RET exon 10, 11, 12, 13, 14, 15 and 16 and immunohistochemistry for RET monoclonal antibody were performed on the archival tissues of 84 cases of sporadic endocrine tumours, including 22 medullary thyroid carcinomas (MTCs), 35 adrenal pheochromocytomas (APCs), 18 paragangliomas (PGs), and nine parathyroid adenomas (PTAs).
  
  
  RESULTS
  PCR-based direct sequencing revealed somatic point missense mutation within 22.7% of exon 13 of the RET proto-oncogene (four cases of E768D, one case of S7781) in MTCs. No RET genotype and morphological association was observed in MTCs or APCs. APCs revealed significantly lower levels of immunoexpression of RET, even versus PGs.
  
  
  CONCLUSIONS
  The genetic mutation in RET is relatively low in incidence, and likely to play an insignificant role in the molecular pathogenesis of sporadic MTC. The molecular bases of PG and APC seem to be different despite their embryological and histological similarities.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea. cho1988@yumc.yonsei.ac.kr
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Lim
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.forename: Wung Yun
authors.initials: WY
authors.lastname: Jung
authors.forename: Chung Su
authors.initials: CS
authors.lastname: Park
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010235:Paraganglioma / Q000235:genetics / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000378:metabolism; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases