Papillary Renal Carcinoma: MET Gene Sequencing

Condition Description

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.

References

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.

Genes (1)

Indications

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

Methodology

Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

Detection

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%

Specimen Requirements

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Saliva
SLV

Requirements
Oragene™ Saliva Collection Kit
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.
Collection and Shipping
Please do not refrigerate or freeze saliva sample. Please store and ship at room temperature.
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
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
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 24 hours of collection. Do not refrigerate or freeze.
DNA, Isolated
DNA

Requirements
Microtainer
8µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
  • 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.

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