Cancer predisposition analysis and post-disclosure behaviors after screening in Japanese children

Germline pathogenic variants in cancer predisposition genes are found in approximately 10% of children with cancer, yet data regarding result disclosure and subsequent clinical actions in Japan remain scarce. To evaluate the frequency of germline pathogenic variants in children and to assess post-disclosure clinical actions, including surveillance and cascade testing in Japan. We retrospectively analyzed 188 patients diagnosed with cancer before age 20 and treated at the University of Tsukuba Hospital. Targeted sequencing panels were applied, supplemented by multiplex ligation-dependent probe amplification or direct sequencing when indicated. Variants were classified according to ACMG/AMP guidelines. Pathogenic or likely pathogenic variants were disclosed to patients and families upon consent, followed by counseling on surveillance and cascade testing. Germline pathogenic variants were identified in 20 patients (10.6%), most frequently in DICER1, TP53, SMARCB1 , and RB1 . Carriers more frequently had a family history of cancer and secondary malignancies (p = 0.001 and p = 0.028, respectively). Results were disclosed in 15 patients; among them, 9 initiated surveillance and cascade testing was performed in 7 families. Surveillance was not implemented when patients had died before disclosure or had not reached the recommended age. Families generally accepted the findings and participated in surveillance, consistent with Western reports. This study is the first in Japan to describe disclosure practices and subsequent actions following germline testing in pediatric cancer patients. Rates of surveillance and cascade testing were comparable to those reported internationally. These findings support incorporating germline testing into standard pediatric oncology care.