Back to Search
Start Over
Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas
- Source :
- Nature genetics. 16(1)
- Publication Year :
- 1997
-
Abstract
- Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumours. The pattern of inheritance of HPRC is consistent with autosomal dominant transmission with reduced penetrance. HPRC is histologically and genetically distinct from two other causes of inherited renal carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation (3;8). Malignant papillary renal carcinomas are characterized by trisomy of chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome. Inherited and sporadic clear cell renal carcinomas are characterized by inactivation of both copies of the VHL gene by mutation, and/or by hypermethylation. We found that the HPRC gene was located at chromosome 7q31.1-34 in a 27-centimorgan (cM) interval between D7S496 and D7S1837. We identified missense mutations located in the tyrosine kinase domain of the MET gene in the germline of affected members of HPRC families and in a subset of sporadic papillary renal carcinomas. Three mutations in the MET gene are located in codons that are homologous to those in c-kit and RET, proto-oncogenes that are targets of naturally-occurring mutations. The results suggest that missense mutations located in the MET proto-oncogene lead to constitutive activation of the MET protein and papillary renal carcinomas.
- Subjects :
- Adult
Male
Genetic Linkage
Urology
Molecular Sequence Data
Hereditary Papillary Renal Cell Carcinoma
Chromosomal translocation
Biology
urologic and male genital diseases
Y chromosome
medicine.disease_cause
Proto-Oncogene Mas
Germline
Germline mutation
Genetics
medicine
Missense mutation
Humans
Amino Acid Sequence
Carcinoma, Renal Cell
Germ-Line Mutation
Aged
Kidney
Mutation
Binding Sites
Sequence Homology, Amino Acid
business.industry
Receptor Protein-Tyrosine Kinases
Middle Aged
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-met
medicine.disease
Penetrance
Carcinoma, Papillary
Kidney Neoplasms
Pedigree
medicine.anatomical_structure
Cancer research
Hereditary leiomyomatosis and renal cell carcinoma
Female
Trisomy
business
Kidney cancer
Chromosomes, Human, Pair 7
Subjects
Details
- ISSN :
- 10614036
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature genetics
- Accession number :
- edsair.doi.dedup.....0ef07a943329c273cbab5ba5bd4649a8