DICER1 tumor predisposition syndrome is a genetic condition that increases the risk of developing certain cancer types. While thyroid tumors are the main tumors caused by this condition in adult oncology, children and adolescents withDICER1germline mutations may suffer from a broader spectrum of tumors, including Sertoli-Leydig cell tumors, pleuropulmonary blastomas, embryonal rhabdomyosarcomas, and pineoblastomas. Although these diseases—many of which are hallmark tumors of DICER1 syndrome and rarely occur sporadically—have been known for several years, the more recent identification ofDICER1mutations in embryonal tumors with multilayered rosettes (ETMR) and DICER1-associated intra- and extracranial sarcomas has expanded the spectrum of tumor types potentially linked to DICER1 syndrome. This review sought to investigate the presence and characteristics ofDICER1mutations in rare CNS tumors and to discuss their potential implications for early recognition ofDICER1-related syndromes. To address this, we conducted a comprehensive systematic literature review and analyzed data from our nationwide German database (CNS-InterREST) regarding these entities. When present,DICER1mutation status, mutation type (somatic vs. germline), and localization within the gene were recorded. Demographic and clinical data—including age at diagnosis and tumor localization—were also evaluated where available. We found that the prevalence ofDICER1mutations in the cohort of ETMR patients included in the CNS-InterREST study was exceedingly low (1/31). The distribution ofDICER1mutations in patients with ETMR or intracranial sarcomas is comparable to that in other previously identifiedDICER1-mutant tumors. Our literature review demonstrates that within the 248 cases, which include three intracranialDICER1-mutated neoplasias and one reference group, most somatic mutations accumulate in the RNase IIIb domain, while germline mutations are usually evenly distributed throughout the gene. Overall, further research is necessary to unravel the cell-of-origin of the respective tumor types and whether other, hitherto undescribed, genetic factors may contribute to the development of ETMR and DICER1-associated intracranial sarcomas.
DICER1肿瘤易感综合征是一种会增加特定癌症患病风险的遗传性疾病。在成人肿瘤学中，甲状腺肿瘤是该疾病引发的主要肿瘤，而携带DICER1种系突变的儿童及青少年可能罹患更广泛的肿瘤谱系，包括支持-间质细胞瘤、胸膜肺母细胞瘤、胚胎性横纹肌肉瘤和松果体母细胞瘤。尽管这些疾病（其中许多是DICER1综合征的标志性肿瘤，散发病例罕见）已被认知多年，但近期在多层菊形团胚胎性肿瘤（ETMR）及DICER1相关颅内/颅外肉瘤中发现的DICER1突变，进一步拓展了可能与DICER1综合征相关的肿瘤类型谱系。本综述旨在探究DICER1突变在罕见中枢神经系统肿瘤中的存在情况及特征，并探讨其对早期识别DICER1相关综合征的潜在意义。为此，我们开展了系统性文献综述，并分析了德国国家数据库（CNS-InterREST）中相关病例的数据。研究记录了DICER1突变状态、突变类型（体细胞突变与种系突变）及基因内定位，同时评估了人口统计学与临床数据（包括诊断年龄与肿瘤定位）。研究发现，在CNS-InterREST研究纳入的ETMR患者队列中，DICER1突变发生率极低（1/31）。DICER1突变在ETMR或颅内肉瘤患者中的分布特征与既往发现的其他DICER1突变肿瘤相似。文献综述显示，在包含3例颅内DICER1突变肿瘤及1个参照组的248例病例中，体细胞突变主要富集于RNase IIIb结构域，而种系突变通常均匀分布于整个基因。总体而言，需要进一步研究以阐明各肿瘤类型的细胞起源，并探索是否存在其他尚未明确的遗传因素参与ETMR及DICER1相关颅内肉瘤的发生发展。
肿瘤(癌症)患者之家