Back to Search Start Over

Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas

Authors :
J. T. Feltis
Hiltrud Brauch
Gladys Glenn
C. Casadevall
McClellan M. Walther
Stefan Storkel
Thomas Stackhouse
Irina A. Lubensky
Ulf S.R. Bergerheim
C. J. M. Lips
Abirami Chidambaram
L. Slife
Peter L. Choyke
Rando Allikmets
B. Zbar
Holger Moch
Stéphane Richard
Lap-Chee Tsui
W.M. Linehan
Laura S. Schmidt
Zhengping Zhuang
Michael Dean
Jochen Decker
J. Lipan
M. Bernues
Fuh Mei Duh
Michael I. Lerman
A. Zamarron
Laura Geil
G. Niehans
Mary Lou Orcutt
Takeshi Kishida
Stephen W. Scherer
M. D. Hughson
F. Chen
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.

Details

ISSN :
10614036
Volume :
16
Issue :
1
Database :
OpenAIRE
Journal :
Nature genetics
Accession number :
edsair.doi.dedup.....0ef07a943329c273cbab5ba5bd4649a8