DICER1syndrome is a hereditary cancer predisposition syndrome, characterized by a large range of benign and malignant neoplasms. Patients withDICER1syndrome have a broad phenotype, with pleuropulmonary blastoma, Sertoli–Leydig cell tumor, cystic nephroma, cervical embryonal rhabdomyosarcoma, cystic lung lesions, and thyroid follicular nodular disease being the most prevalent manifestations. The syndrome is caused by loss-of-function germline variants in theDICER1gene, andDICER1-related tumors are characterized by second somatic hotspot variants in the RNase IIIb domain ofDICER1.DICER1encodes an endoribonuclease, which is important for RNA interference. This review describes the molecular mechanism ofDICER1function and the pathogenetic mechanisms of tumorigenesis. The purpose of this review is to describe the pathogenesis, genotype–phenotype correlation and tissue specificity ofDICER1syndrome. We conclude that there is a lack of knowledge about the exact molecular mechanisms ofDICER1function and more research is needed to determine the exact role of this altered protein in relation to pathogenesis.
DICER1综合征是一种遗传性癌症易感综合征，其特征表现为广泛的良性和恶性肿瘤谱。该综合征患者临床表现多样，其中胸膜肺母细胞瘤、支持-间质细胞瘤、囊性肾瘤、宫颈胚胎性横纹肌肉瘤、肺囊性病变及甲状腺滤泡结节性疾病最为常见。该综合征由DICER1基因功能缺失性种系变异引起，其相关肿瘤的特征在于DICER1基因RNase IIIb结构域存在继发性体细胞热点变异。DICER1基因编码的内切核糖核酸酶对RNA干扰至关重要。本综述阐述了DICER1功能的分子机制及其致瘤的病理机制，旨在系统论述DICER1综合征的发病机制、基因型-表型相关性及组织特异性。我们得出结论：目前对DICER1功能的具体分子机制认知尚不充分，需进一步研究以明确该变异蛋白在发病机制中的确切作用。
DICER1Syndrome: What Do We Know of the Pathogenetic Mechanisms?
肿瘤(癌症)患者之家