Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, Quebec, Canada.
Hum Mutat. 2011 Dec;32(12):1381-4. doi: 10.1002/humu.21600. Epub 2011 Oct 11.
DICER1 is crucial for embryogenesis and early development. Forty different heterozygous germline DICER1 mutations have been reported worldwide in 42 probands that developed as children or young adults, pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors (especially Sertoli-Leydig cell tumor [SLCT]), and/or multinodular goiter (MNG). We report DICER1 mutations in seven additional families that manifested uterine cervix embryonal rhabdomyosarcoma (cERMS, four cases) and primitive neuroectodermal tumor (cPNET, one case), Wilms tumor (WT, three cases), pulmonary sequestration (PS, one case), and juvenile intestinal polyp (one case). One carrier developed (age 25 years) a pleomorphic sarcoma of the thigh; another carrier had transposition of great arteries (TGA). These observations show that cERMS, cPNET, WT, PS, and juvenile polyps fall within the spectrum of DICER1-related diseases. DICER1 appears to be the first gene implicated in the etiology of cERMS, cPNET, and PS. Young adulthood sarcomas and perhaps congenital malformations such as TGA may also be associated.
DICER1 对于胚胎发生和早期发育至关重要。全世界已有 42 名患儿或青年期发病的先证者报道了 40 种不同的种系 DICER1 突变，这些患者发生了肺胸膜胚细胞瘤（PPB）、囊性肾瘤（CN）、卵巢性索-间质肿瘤（尤其是 Sertoli-Leydig 细胞瘤[SLCT]）和/或多结节性甲状腺肿（MNG）。我们报道了另外 7 个家系存在 DICER1 突变，这些家系的临床表现为子宫颈胚胎性横纹肌肉瘤（cERMS，4 例）和原始神经外胚层肿瘤（cPNET，1 例）、Wilms 瘤（WT，3 例）、肺隔离症（PS，1 例）和青少年肠息肉（1 例）。1 个携带者（25 岁）发生了大腿多形性肉瘤；另一个携带者患有大动脉转位（TGA）。这些观察结果表明，cERMS、cPNET、WT、PS 和青少年息肉属于 DICER1 相关疾病谱。DICER1 似乎是第一个与 cERMS、cPNET 和 PS 病因相关的基因。青年期肉瘤，以及可能的先天性畸形，如 TGA，也可能与之相关。
