Duplication of the mutant RET allele in trisomy 10 or loss of the wild-type allele in multiple endocrine neoplasia type 2-associated pheochromocytomas.
Inherited mutations of the RET proto-oncogene are tumorigenic in patients with multiple endocrine neoplasia type 2 (MEN 2). However, it is not understood why only few of the affected cells in the target organs develop into tumors. Genetic analysis of nine pheochromocytomas from five unrelated patients with MEN 2 showed either duplication of the mutant RET allele in trisomy 10 or loss of the wild-type RET allele. Our results suggest a "second hit" causing a dominant effect of the mutant RET allele, through either duplication of the mutant allele or loss of the wild-type allele, as a possible mechanism for pheochromocytoma tumorigenesis in patients with MEN 2.
Huang
S C
SC
Molecular Pathogenesis Unit, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
Koch
C A
CA
Vortmeyer
A O
AO
Pack
S D
SD
Lichtenauer
U D
UD
Mannan
P
P
Lubensky
I A
IA
Chrousos
G P
GP
Gagel
R F
RF
Pacak
K
K
Zhuang
Z
Z
D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000483:Alleles; D002879:Chromosomes, Human, Pair 10; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D029721:Drosophila Proteins; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014314:Trisomy
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