Papillaryrenal tumors, which account for 15 to 20% of renal carcinomas, occur in bothsporadic and familial forms. Hereditary papillary renalcarcinoma (HPRC) is an autosomal dominant hereditary cancer syndrome in whichaffected individuals are at risk of developing bilateral, multifocal type 1papillary renal carcinoma, often at a late age of onset (50 to 70 years). Todate, the kidney is the only organ to be affected in HPRC patients. The tumorsare most often well differentiated; however, they are malignant and canmetastasize. HPRC is a highly penetrant disease in which affected individualsare highly likely to develop bilateral, multifocal type 1 papillary kidneycancer. In the early reports, this disease was described as having a late onset;however, recently an early onset form of this disease has been described.
Germlinemutations in the MET gene on chromosome 7 were identified ina hereditary form of papillary renal carcinoma. MET belongs to thefamily of tyrosine kinases, the members of which play important rolesin transmitting signals from the cellular surface to the nucleus. Missense mutations in the tyrosine kinase domain of the Met proto-oncogene at 7q31 are responsible for constitutive activation of the METprotein in HPRC.
For patients with suspected hereditary papillary renalcarcinoma, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
Bodmer, D. et al. Understandingfamilial and non-familial renal cell cancer. 2002. Hum. Molec.Genet. 11: 2489-2498.
Rosner, I. et al. The clinicalimplications of the genetics of renal cell carcinoma. 2009. Urol. Oncol. 27(2):131-136.
Click here for the OMIM summary on this condition.
This test is indicated for:
- Confirmation of a clinical diagnosis of hereditary papillary renal carcinoma
- Individuals at-risk for hereditary papillary renal carcinoma due to family history
Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's biochemical phenotype.
Analytical Sensitivity: ~99%
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
- Deletion/duplication analysis of the MET gene by CGH array is available for those individuals in whom sequence analysis is negative (UY).
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.