Molecular genetics tumor board
December 30, 2015
The purpose of the tumor board is to provide a multidisciplinary review of somatic (tumor) testing for the purposes of clarifying the potential implications of a patient’s results. This includes but is not limited to: prognosis, additional therapeutics, available clinical trials, and possible incidence of underlying hereditary cancer predisposition syndromes. The American College of Medical Genetics (ACMG), American Society of Clinical Oncology (ASCO), and Association for Molecular Pathology (AMP) all recommend multidisciplinary review of somatic genetic testing to bridge the inevitable gap in knowledge between those closely involved with genomic data, such as molecular pathologists and genetics providers, and health care providers, such as surgeons and medical oncologists. Providers would otherwise be hard pressed to keep up with new developments, but they need to integrate this information into their medical practice for optimal care of their patients.
With genome testing by next generation sequencing technologies, perceived and real potential risks are magnified compared with genetic testing that targets only one gene at time. There are also unique challenges to somatic genetic testing compared to the “traditional” germline genetic tests with which providers are generally more familiar. Reporting pipelines for these tests are very different from those providers are used to. In addition, while the testing is performed primarily for reasons such as prognosis and treatment, it must be understood that there is a very real possibility of uncovering an underlying hereditary cancer predisposition syndrome that would have other health implications for not only the patient but also his or her family members.
A recent study by UC San Diego researchers reported that 66 percent of patients whose tumors were tested with NGS had at least one sequence variant in a gene associated with a hereditary cancer predisposition syndrome and 24 percent of patients undergoing somatic tumor testing would be considered appropriate for referral for germline genetic testing. When a variant is reported in a gene that is associated with an underlying hereditary cancer predisposition syndrome on a somatic tumor test, steps should be taken to consider whether followup germline genetic testing needs to be performed. This may include assessing the patient’s clinical and family history and the potential pathogenicity of the variant.
It should never be assumed that a patient is negative simply because a variant is not reported in a hereditary cancer predisposition gene when the patient’s history is consistent with a syndrome. True deleterious mutations in hereditary predisposition genes may be absent from the report because the reporting pipeline is designed to deliver only potentially actionable somatic results. The molecular tumor board, regularly attended by treating oncologists, molecular pathologists, and genetic counselors, provides a means for providers to review and discuss somatic test reports with other treating clinicians and specialists to ensure the most accurate interpretation and clinical implementation of the test reports take place.