Research Unit Pediatric Hematology and Immunology.
Institute for Medical Informatics, Statistics, and Documentation.
Curr Opin Pediatr. 2018 Dec;30(6):855-863. doi: 10.1097/MOP.0000000000000680.
The risk of cancer is higher, and its outcome is worse in patients with primary immunodeficiency (PID) than in members of the general population. Thus, the inter-relationship of malignant diseases with PIDs requires more study.
Large genetic screens identified a vast number of germline mutations in childhood cancer patient samples. Although TP53 was the most frequent single gene identified as mutated, many PID disorders like DNA repair defects are among the inborn causes of childhood cancer. We provide a comprehensive analysis of compiled data from seven recent studies that focused on germline genetic landscapes and preexisting conditions in pediatric oncology. As potentially causal germline variants were identified in ≈8% of malignancies in children and adolescents, we visualized this proportion as the 'tips of the icebergs'. The results of additional network analyses showed the shared patterns of germline mutations in various malignancies and yielded a spatial distribution of the 'icebergs'.
The 'iceberg map of germline mutations in childhood cancers' was created to increase the awareness of the inborn genetic underpinnings of childhood malignancies and their relationships with immunodeficiencies. Needs and perspectives of clinical immunologists and pediatric oncologists to both improve patient care and guide research at this critical interface are discussed. VIDEO ABSTRACT.
目的综述：原发性免疫缺陷（PID）患者的癌症风险更高，且预后更差。因此，PID 与恶性疾病之间的相互关系需要进一步研究。
最新发现：大规模的基因筛查在儿童癌症患者样本中发现了大量的胚系突变。虽然 TP53 是最常见的突变单一基因，但许多 PID 疾病（如 DNA 修复缺陷）也是儿童癌症的先天原因之一。我们对最近的七项研究进行了综合分析，这些研究主要集中在儿科肿瘤学中的胚系遗传图谱和潜在病症。由于约 8%的儿童和青少年恶性肿瘤中存在潜在因果关系的胚系变异，我们将这一比例视为“冰山一角”。进一步的网络分析结果显示，各种恶性肿瘤中存在共同的胚系突变模式，并产生了“冰山”的空间分布。
总结：本研究绘制了“儿童癌症胚系突变冰山图”，旨在提高人们对儿童恶性肿瘤先天遗传基础及其与免疫缺陷关系的认识。讨论了临床免疫学家和儿科肿瘤学家的需求和观点，以改善患者的治疗效果并指导这一关键领域的研究。
