Germline RET mutations in MEN 2A and FMTC and their detection by simple DNA diagnostic tests.
Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are two closely related cancer syndromes inherited in an autosomal dominant manner. Mutations in the RET proto-oncogene were found in MEN 2A and FMTC families. In this study we report seven different germline mutations in the RET proto-oncogene in five of five MEN 2A and five of six FMTC families. Each of the mutations involves a cysteine residue in the extracellular cysteine-rich domain of the RET receptor tyrosine kinase. We developed simple polymerase chain reaction based diagnostic tests for all seven mutations in these families.
Xue
F
F
Department of Human Genetics and Molecular Biology, Collaborative Research, Inc., Waltham, MA 02154.
Yu
H
H
Maurer
L H
LH
Memoli
V A
VA
Nutile-McMenemy
N
N
Schuster
M K
MK
Bowden
D W
DW
Mao
J
J
Noll
W W
WW
D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics*; D003545:Cysteine; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D006580:Genetic Carrier Screening; D006801:Humans; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; 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*; D013964:Thyroid Neoplasms / Q000235:genetics*
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; D003545:Cysteine