Multiple endocrine neoplasia type 2-associated RET proto-oncogene mutations do not contribute to the pathogenesis of sporadic parathyroid tumors.
BACKGROUND
Parathyroid disease occurs sporadically or as part of hereditary multiple endocrine neoplasia (MEN) syndrome. The aim of this study was to evaluate the possible role of the RET proto-oncogene not only in hereditary MEN 2-associated hyperparathyroidism but also in different forms of sporadic hyperparathyroidism.


METHODS
We investigated 22 patients with parathyroid disease whose family history and results of laboratory and clinical examinations excluded MEN 2 syndrome. DNA extractions of histologically confirmed tumor tissue of patients with primary hyperparathyroidism (n = 18), renal hyperparathyroidism (n = 2), and parathyroid carcinoma (n = 2) were performed. Using solid phase DNA sequencing, mutation analysis of polymerase chain reaction amplified products focused on exons 10, 11, and 16 of the RET proto-oncogene. Parathyroid tissue from four patients with known MEN 2A served as positive controls.


RESULTS
No mutations of the codons 609, 611, 618, 620, 634, and 918 were found in the sporadic parathyroid tumors analyzed. DNA sequencing revealed heterozygous mutations in codon 634 of the RET proto-oncogene in four parathyroid glands from four patients with MEN 2A.


CONCLUSIONS
Mutations of the RET proto-oncogene contributing to MEN 2 syndromes are absent in sporadic parathyroid tumors. Our data in conjunction with the literature suggest at least three different modes of tumorigenesis in parathyroid disease.
Willeke
F
F
Department of Surgery, Ruprecht Karls University of Heidelberg, Germany.
Hauer
M P
MP
Buchcik
R
R
Gebert
J F
JF
Hahn
M
M
Fitze
G
G
Mechtersheimer
G
G
Möller
P
P
Saeger
H D
HD
Herfarth
C
C
Schackert
H K
HK
D000236:Adenoma / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications* / Q000235:genetics; D010282:Parathyroid Neoplasms / Q000209:etiology / Q000235:genetics*; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D004273:DNA, Neoplasm; 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