Laboratories develop panels of genes to evaluate risk for different types of hereditary cancers. Each laboratory examines different genes on its panels, and there is currently no standard of which genes should be evaluated for a given type of cancer.
Unlike traditional genetic testing, which involves analyzing a single gene with Sanger sequencing and MLPA analysis for deletions and duplications, next-generation sequencing (NGS) allows for the simultaneous sequencing of multiple genes. NGS tests generally target the coding exons of the genes of interest, as well as a small portion of the flanking exons. MLPA analysis is still needed to detect deletions and duplications.
NGS panels can include five to 50 or more genes and can range in price from approximately $1,000 to $5,000. There are a variety of panel-testing options at laboratories throughout the country. These include cancer-site-specific and general cancer panels. Additionally, some laboratories have options of smaller panels with clinically actionable information only. Please contact one of our genetic counselors if you have questions regarding available testing options.
One limitation of NGS testing is that a disease-causing alteration could occur outside the region captured by the test. NGS testing is most useful when testing an affected patient who has a history that is suggestive of more than one gene.
Some of the genes evaluated on NGS panels are moderate-risk genes. Currently, consensus guidelines have not been established for clinical management of moderate-risk genes. Clinicians’ understanding of the types of cancers associated with these genes and the level of risk will evolve over time.
At this point, NGS panels have a high yield of uncertain results (variants of uncertain significance).
Because of the limitations, the paucity of clinical management guidelines, and the increased likelihood of uncertain results, patients should be carefully counseled prior to having NGS testing. NCCN guidelines state: “Cancer risk assessment and genetic counseling is highly recommended when genetic testing is offered (i.e., pre-test counseling) and after results are disclosed (i.e., post-test counseling)” (Genetic/Familial High Risk Assessment: Breast and Ovarian Version 2.2015).