How to manage patients when a germline pathogenic variant (germline mutation) is identified

Abstract

When germline mutations are identified by a cancer multigene panel test on pediatric hematologic oncology, the guidelines for disclosure of secondary findings in multigene panel tests for solid tumors can be used as a reference. It is desirable to note the difference in clinical actionability of the hematology/oncology panel, which aims to not only identify therapeutic targets but also diagnose and predict prognosis. Information on germline mutations is useful in clinical settings. For instance, germline variants in TP53 that cause Li-Fraumeni syndrome (LFS) are a risk factor for the development of second cancers and are useful information to determine the indication for radiation therapy. Guidelines for the management of LFS have been established, cancer surveillance trials have been initiated, and follow-up methods are being established. Clinical guidance describing surveillance methods has also been published for other pediatric cancer predisposition syndromes. Parents and siblings of the patients who have the germline mutation of the hereditary tumor are at 50% risk of carrying the identical mutation. If the patient is a young child, the parent may develop cancer later in life. The indication for genetic testing of siblings should consider the age of onset of the tumor. To make effective use of germline mutation information in clinical practice, we as healthcare professionals need to be aware of the social, psychological, and ethical circumstances surrounding patients with cancer predisposition.