Cancer predisposition genes in Japanese children with rhabdomyosarcoma

Background: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas in children. Germline mutations in cancer predisposition genes have been detected in approximately 10% of pediatric cancers. However, the genetic background of RMS is still unclear, especially in Asian children. Procedure: DNA was extracted from the peripheral blood of children with RMS and cancer-associated genes analyzed using targeted re-sequencing. Results: Twenty patients participated in this study. The median age at diagnosis was 5.0 years. The male-to-female ratio was 3:2. There were three deaths due to RMS. One patient developed a second neoplasm. Nine patients had long-term co-morbidities. Five pathogenic variants were found in four patients: one nonsense variant of DICER1, one exon deletion of TP53, and three missense variants of LIG4 and MEN1. Two of the four patients had a family history of cancer. Two patients with missense variants of LIG4 had long-term co-morbidities of drug-induced cardiomyopathy. This is the first report of germline cancer-related gene variants with detailed clinical information in Japanese children with RMS. The missense variants of LIG4, essential for DNA double-strand break repair, were detected in two unrelated patients. Conclusions: When this is the first report of the germline genetic analysis of Japanese children with RMS, the frequency of the variant was almost equivalent to that of previous reports from Western countries. Unbiased exon sequencing may be useful to clarify the pathogenesis of RMS in children and in predicting the clinical course of these patients.