Department of Pediatrics, University of Tsukuba Hospital, Ibaraki, Japan.
Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Oncology. 2022;100(3):163-172. doi: 10.1159/000521621. Epub 2021 Dec 27.
Brain tumors affect one-third of all children with cancer. Approximately 10% of children with cancer carry variants in cancer-predisposition genes. However, germline analyses in large cohorts of Asian children have not been reported. Thirty-eight Japanese patients with pediatric brain tumors were included in this study (19 boys, 19 girls). DNA was extracted from the patients' peripheral blood, and cancer-associated genes were analyzed using targeted resequencing. Rare variants with allele frequencies <0.1% in the general population and variants suspected to be pathogenic were extracted and analyzed. Pathogenic variants were found in 7 patients (18%): 2 nonsense variants of CHEK2 and FANCI; 2 frameshift deletions in SMARCB1 and PTCH1; and 3 missense variants of TSC1, WRN, and MLH1. The median age at diagnosis was 9.1 years, and three of the 7 patients had a family history of cancer. One patient diagnosed with basal cell nevus syndrome, also called Gorlin syndrome, developed a second neoplasm, and another with an SMARCB1 variant and an atypical teratoid/rhabdoid tumor developed a thyroid adenomatous nodule. This is the first cancer-related germline analysis with detailed clinical information reported in Japanese children with brain tumors. The prevalence was almost equivalent to that in white children.
脑肿瘤影响所有癌症患儿的三分之一。大约 10%的癌症患儿携带有癌症易感基因的变异。然而，亚洲儿童的大型队列的种系分析尚未报道。本研究纳入了 38 名患有小儿脑肿瘤的日本患者（男 19 例，女 19 例）。从患者外周血中提取 DNA，并使用靶向重测序分析与癌症相关的基因。提取并分析了在普通人群中等位基因频率<0.1%的罕见变异和疑似致病性的变异。在 7 名患者（18%）中发现了致病性变异：2 名 CHEK2 和 FANCI 的无义变异；2 名 SMARCB1 和 PTCH1 的框移缺失；以及 TSC1、WRN 和 MLH1 的 3 个错义变异。诊断时的中位年龄为 9.1 岁，7 名患者中有 3 名有癌症家族史。一名诊断为基底细胞痣综合征（也称为 Gorlin 综合征）的患者发生了第二种肿瘤，另一名携带 SMARCB1 变异和非典型畸胎瘤/横纹肌样瘤的患者发生了甲状腺腺瘤性结节。这是首次在日本脑肿瘤患儿中报告的具有详细临床信息的癌症相关种系分析。其患病率与白人儿童几乎相当。
