Somatic mutations of the RET proto-oncogene are not required for tumor development in multiple endocrine neoplasia type 2 (MEN 2) gene carriers.
Germ line mutations in one allele of the RET proto-oncogene predispose to the multiple endocrine neoplasia type 2 (MEN 2) syndromes. To investigate whether these inherited mutations alone can cause the development of tumors in vivo (oncogene model) or whether somatic mutations in the homologous RET allele are required for tumorigenesis (tumor suppressor gene model), we analyzed the entire coding region of both alleles of the RET gene in two MEN 2A and two MEN 2B tumors by reverse transcription-PCR and direct sequencing. No tumor-specific mutations could be detected in either allele of the RET gene in these tumors. Unlike the molecular mechanism in other hereditary tumor syndromes, somatic mutations in the homologous allele are apparently not required in MEN 2 tumorigenesis. Thus, RET genes with MEN 2-specific germ line mutations act as dominantly transforming oncogenes in vivo.
Landsvater
R M
RM
Department of Internal Medicine, University Hospital Utrecht, the Netherlands. R.M.Landsvater@lab.azu.nl.
de Wit
M J
MJ
Zewald
R A
RA
Hofstra
R M
RM
Buys
C H
CH
Ploos van Amstel
H K
HK
Höppener
J W
JW
Lips
C J
CJ
D018076:DNA, Complementary / Q000737:chemistry; D029721:Drosophila Proteins; D006579:Heterozygote; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D018076:DNA, Complementary; 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