AUTS9; DFNB97; HGFR; RCCP2; c-Met
The MET gene is associated with autosomal dominant hereditary papillary renal cell carcinoma (HPRCC) (MedGen UID: 766).
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Invitae tests that include this gene:
The MET gene is an oncogene that encodes a tyrosine kinase and is the cell surface receptor for hepatocyte growth factor.
Hereditary papillary renal cell carcinoma
MedGen UID: 766
Renal cell carcinoma (RCC) is the most common cancer of the kidney (PMID: 26052049). Papillary renal cell carcinoma (PRCC) accounts for 10–15% of all renal cell cancers (PMID: 25905938). Although most cases are sporadic, it is believed that 2–5% of renal cancers are due to an underlying hereditary cancer syndrome (PMID: 25905938), 26559379). A small, unspecified number of these hereditary cases are due to hereditary papillary renal cell carcinoma (HPRCC). HPRCC is a highly penetrant, rare, autosomal dominant condition associated with a predisposition to developing type 1 papillary renal cell carcinoma that is typically bilateral and multifocal. Nearly everyone with a disease-causing pathogenic variant in the MET gene will express the condition; however, there are no other organ systems or clinical features associated with this adult-onset disorder that, on average, presents at approximately age 50 (PMID: 25905938, 23882344, 24710684, 26052049, 26559379, 9563489, 12647800, 8308957).
MET is a proto-oncogene associated with the hepatocyte growth factor receptor and encodes tyrosine-kinase activity (NCBI Gene. Gene ID: 4233. http://www.ncbi.nlm.nih.gov/gene/4233. Accessed March 2016). If there is a pathogenic variant in this gene that prevents it from functioning normally, there may be an increased risk of developing certain types of cancer.
Hereditary papillary renal cell carcinoma has autosomal dominant inheritance. This means that an individual with a pathogenic variant in MET has a 50% chance of passing the condition on to their offspring. With this result, it is now possible to identify at-risk relatives who can pursue testing for this specific familial variant. Many cases are inherited from a parent, but some cases can occur spontaneously (i.e., an individual with a pathogenic variant has parents who do not have it).
While there are currently no established medical management and surveillance guidelines, the following has been proposed (PMID: 23882344):
An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.
Even though data regarding MET is preliminary, knowing if a pathogenic variant is present is advantageous. At-risk relatives can be identified, enabling pursuit of a diagnostic evaluation. Further, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant data regarding MET are likely to become available in the near future. Awareness of this cancer predisposition encourages patients and their providers to inform at-risk family members, to consider implementing proposed screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.
Review Date: March 2016
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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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|