Hereditary papillary renal cell carcinoma

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Hereditary papillary renal cell carcinoma

Identity

Note

other (well known) classes of inherited renal cell carcinomas are:

the Von Hippel-Lindau syndrome, and

the Lynch syndrome II

Inheritance

some familly trees resemble autosomal recessive transmission (affected sibs with unaffected parents), other exhibit typical autosomal dominant trasmission with a vertical parent-to-child pattern; the situation is not that of (recessive) tumour suppressor genes as in the retinoblastoma, nor that of a recessive DNA replication/repair gene like in Bloom's, but the overexpression of the mutant allele through (acquired) chromosome imbalance (see below)

Clinics

Note	no phenotypic sign
Neoplastic risk	multiple and/or bilateral papillary renal cell carcinomas, with median age 45 yrs at diagnosis (range 18-79 yrs, most cases being between 35 and 55 yrs old), sex ratio 29M/12F, the presence of asymptomatic cases (mutations have also been detected in tumour-free individuals in these pedigrees pointing to a low expressivity), and still a median age at death of affected individuals at 52 yrs

Cytogenetics

Note	similar to what is found in sporadic papillary renal cell carcinoma, in particular trisomy 7 and 17

Other findings

Note	no loss of heterozygosity at loci on 3p in the tumours; this contrasts with clear-cell renal cell carcinomas which are associated with deletions of 3p

Genes involved and Proteins

Gene Name	MET
Location	7q31

Protein
Expression	wide
Localisation	membrane
Function	transmembrane tyrosine kinase receptor for the hepatocyte growth factor/scatter factor (HGF/SF)

Mutations
Germinal	found mutated in half of the cases of hereditary papillary renal cell carcinoma so far studied; mutations were in exons 16-19 (tyrosine kinase domain); cases without a detected mutation may either have a mutation in non-tested parts of MET, or mutations in another gene
Somatic	the mutant MET allele is duplicated (via the trisomy 7) in the tumours; might lead to a constitutive kinase activation

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