Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene.
Cancer Res
; 58(8): 1719-22, 1998 Apr 15.
Article
in En
| MEDLINE
| ID: mdl-9563489
ABSTRACT
Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited disorder characterized by a predisposition to develop multiple bilateral papillary renal carcinomas. Individuals affected with HPRC have been shown to have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene. We identified a novel mutation in exon 16 of the MET gene in two large North American HPRC families. The H1112R MET mutation segregated with the disease, was not present in 320 normal chromosomes, and caused malignant transformation of NIH 3T3 cells. By examining individuals with the H1112R mutation, we determined the age-dependent penetrance of this mutation and identified additional nonrenal malignancies that occurred in mutation carriers. Affected members of the two families shared the same haplotype within and immediately distal to the MET gene, suggesting a founder effect. The identification of the H1112R mutation will facilitate predictive testing in HPRC and guide future studies of the MET gene in human neoplasia.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Papillary
/
Proto-Oncogene Proteins c-met
/
Kidney Neoplasms
/
Mutation
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
America do norte
Language:
En
Journal:
Cancer Res
Year:
1998
Type:
Article
Affiliation country:
United States