Associated disorders

The MET gene is associated with autosomal dominant hereditary papillary renal cell carcinoma (HPRCC) (MedGen UID: 766).

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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

Clinical condition
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).

Gene information
MET is a proto-oncogene associated with the hepatocyte growth factor receptor and encodes tyrosine-kinase activity (NCBI Gene. Gene ID: 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):

  • CT scan with intravenous contrast over ultrasound as the main modality for diagnosis and follow-up
  • Treatment options that may include close observation in those cases where the mass is less than 3 cm in largest diameter to nephron-sparing surgery, or partial nephrectomy for larger tumors
  • Cryoablation and minimally invasive radiofrequency ablation as an alternative for small or multiple tumors

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

Assay and technical information

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
MET NM_001127500.1