DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association
DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association
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DOI：
10.1210/jc.2015-2169
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发表时间：
2016-01-01
影响因子：
5.8
通讯作者：
Hill, D. Ashley
中科院分区：
文献类型：
--
作者：
Rutter, Meilan M.;Jha, Pranati;Hill, D. Ashley
内容：DICER 1生殖系突变携带者具有增加的癌症易感性，例如胸膜肺母细胞瘤（PPB）和Sertoli-Leydig细胞瘤（SLCT），以及多结节性甲状腺肿（MNG）的高患病率。虽然分化型甲状腺癌（DTC）已报告在一些DICER 1突变携带者与PPB治疗化疗，DTC与DICER 1突变的协会是不好established.Case描述：我们报告一个家庭与DICER 1突变和家族性DTC没有化疗史。一名12岁的女性（患者A）和她14岁的妹妹（患者B）患有MNG。值得注意的家族史是DTC和双侧卵巢SLCT的母亲病史。两姐妹篇都接受了甲状腺全切除术。病理检查示结节性增生，增生结节内有局灶性甲状腺乳头状癌。随后，患者A发生继发于单侧卵巢SLCT的男性化。在她的评估中，还发现了一个偶然的囊性肾瘤。另外三个兄弟姐妹在监测超声检查中有MNG;两个甲状腺切除术，一个有两个乳头状癌的显微镜病灶。患者A、她的母亲和四个受影响的兄弟姐妹在外显子25中具有生殖系杂合致病性DICER 1突变c.5441C>T，导致DICER 1的p.Ser1814Leu的氨基酸改变。体细胞DICER 1 RNase IIIb错义突变被确定在甲状腺结节从三个四siblings.Conclusions：这个家庭提供了新的见解DICER 1综合征的一个新兴的表型，有证据表明，生殖系DICER 1突变与发展家族性DTC的风险增加，即使在没有事先治疗与化疗。
Context: DICER1 germline mutation carriers have an increased predisposition to cancer, such as pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT), and a high prevalence of multinodular goiter (MNG). Although differentiated thyroid carcinoma (DTC) has been reported in some DICER1 mutation carriers with PPB treated with chemotherapy, the association of DTC with DICER1 mutations is not well established.Case Description: We report a family with DICER1 mutation and familial DTC without a history of chemotherapy. A 12-year-old female (patient A) and her 14-year-old sister (patient B) presented with MNG. Family history was notable for a maternal history of DTC and bilateral ovarian SLCT. Both sisters underwent total thyroidectomy. Pathological examination showed nodular hyperplasia and focal papillary thyroid carcinoma within hyperplastic nodules. Subsequently, patient A developed virilization secondary to a unilateral ovarian SLCT. During her evaluation, an incidental cystic nephroma was also found. Three other siblings had MNG on surveillance ultrasound examination; two had thyroidectomies, and one had two microscopic foci of papillary carcinoma. Patient A, her mother, and four affected siblings had a germline heterozygous pathogenic DICER1 mutation c.5441C>T in exon 25, resulting in an amino acid change from p.Ser1814Leu of DICER1. Somatic DICER1 RNase IIIb missense mutations were identified in thyroid nodules from three of the four siblings.Conclusions: This family provides novel insight into an emerging phenotype for DICER1 syndrome, with evidence that germline DICER1 mutations are associated with an increased risk of developing familial DTC, even in the absence of prior treatment with chemotherapy.