This test analyzes the MET gene, which is associated with hereditary papillary renal cell carcinoma (HPRCC). This highly penetrant, rare, autosomal-dominant condition causes a predisposition to developing type 1 papillary renal cell carcinoma that is typically bilateral and multifocal. HPRCC is an adult-onset condition with an average age of onset of 50 years.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
The general population risk of developing kidney cancer is approximately 1.6%. Papillary renal cell carcinoma (PRCC) accounts for 10%–20% of all renal cell cancers. Although most cases are sporadic, it is believed that 1%-4% of renal cancers are due to an underlying hereditary cancer syndrome. A small but currently unknown number of these hereditary cases is due to hereditary papillary renal cell carcinoma (HPRCC). This highly penetrant, rare, autosomal-dominant condition is associated with a predisposition to developing type 1 papillary renal cell carcinoma that is typically bilateral and multifocal. There are no other organ systems or clinical features associated with this condition. HPRCC is an adult-onset condition with an average age of onset of 50 years.
Most individuals with a pathogenic variant in MET will express the condition and manifest symptoms of HPRCC. The lifetime risk of renal cancer for individuals with HPRCC approaches 100%.
Most cases are inherited in an autosomal dominant pattern, although the rate of spontaneous de novo mutations is unknown.
Individuals—particularly adults—presenting with papillary renal carcinoma may be considered for analysis of the MET gene.
For management recommendations, please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|