[Mechanism of carcinogenesis by germline mutation of protooncogene in hereditary tumors].
Germline mutations in one of two alleles of c-ret, c-met and c-kit protooncogenes have been revealed to be the causes of three autosomal dominant hereditary tumors; multiple endocrine neoplasia type 2(MEN2), hereditary papillary renal cell carcinoma (HPRCC), and familial gastrointestinal stromal tumor(FGIST), respectively. Patients with MEN2A have missense mutations at extracellular cysteine rich domain of c-ret, those with MEN2B have missense mutations at tyrosine kinase domain of c-ret, those with HPRCC have missense mutations at tyrosine kinase domain of c-met, and those with FGIST have in-frame deletion mutations at juxtamembrane domain of c-kit. All of these mutations are assumed to cause constitutive activation of protooncogenes without binding to ligands, resulting in tumor formation.
Miyaki
M
M
Tokyo Metropolitan Komagome Hospital.
D000483:Alleles; D003545:Cysteine; D005799:Genes, Dominant / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D020125:Mutation, Missense; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D011519:Proto-Oncogenes / Q000235:genetics*
D011505:Protein-Tyrosine Kinases; D003545:Cysteine