Genetic aberrance of sporadic MEN 2A component tumours: analysis of RET

Pathology. 2005 Feb;37(1):10-3. doi: 10.1080/00313020400024816.

Abstract

Aim: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / genetics
  • Adrenal Gland Neoplasms / metabolism
  • Adult
  • Base Sequence
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multiple Endocrine Neoplasia / genetics*
  • Multiple Endocrine Neoplasia / metabolism
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Paraganglioma / genetics
  • Paraganglioma / metabolism
  • Parathyroid Neoplasms / genetics
  • Parathyroid Neoplasms / metabolism
  • Pheochromocytoma / genetics
  • Pheochromocytoma / metabolism
  • Point Mutation
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism

Substances

  • Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases