Genetic aberrance of sporadic MEN 2A component tumours: analysis of RET.
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.
Cho
Nam Hoon
NH
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea. cho1988@yumc.yonsei.ac.kr
Lee
Hyun Woo
HW
Lim
Shin Young
SY
Kang
Suki
S
Jung
Wung Yun
WY
Park
Chung Su
CS
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
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