Nat Genet  1997 May;16(1):68-73 

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

Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z,
Lubensky I, Dean M, Allikmets R, Chidambaram A, Bergerheim UR, Feltis JT,
Casadevall C, Zamarron A, Bernues M, Richard S, Lips CJ, Walther MM, Tsui LC,
Geil L, Orcutt ML, Stackhouse T, Zbar B, et al.

Intramural Research Support Program, SAIC Frederick, MD, USA.

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.

PMID: 9140397 [PubMed - indexed for MEDLINE]