Germ-line DICER1 mutations do not make a major contribution to the etiology of familial testicular germ cell tumours.
Germ-line DICER1 mutations do not make a major contribution to the etiology of familial testicular germ cell tumours.
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DOI：
10.1186/1756-0500-6-127
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发表时间：
2013-04-01
影响因子：
1.8
通讯作者：
Foulkes WD
中科院分区：
文献类型：
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作者：
Sabbaghian N;Bahubeshi A;Shuen AY;Kanetsky PA;Tischkowitz MD;Nathanson KL;Foulkes WD
RNase III 酶 DICER1 在 microRNA 的成熟过程中发挥着核心作用。 DICER1 中与肿瘤相关的种系和体细胞突变的鉴定表明，癌症中 miRNA 的错误表达可能是由于其加工缺陷造成的。最近对 96 例睾丸生殖细胞肿瘤中的 DICER1 RNase III 结构域进行的研究的一部分，在精原细胞瘤中发现了单个 RNase IIIb 结构域突变。为了进一步探讨 DICER1 突变在睾丸生殖细胞肿瘤 (TGCT) 病因学中的重要性，我们研究了 43 名诊断患有家族性 TGCT 的先证者的生殖系 DNA 样本。我们对 DICER1 外显子 2-12、14-19、21 和 24-27 进行了高分辨率熔解曲线分析。所有有问题的熔解曲线均经过验证性桑格测序。桑格测序用于外显子 13、20、22 和 23。内含子-外显子边界包含在所有分析中。我们鉴定了 12 个先前报道的单核苷酸多态性和两个新的单核苷酸变异。没有发现可能有害的变异；值得注意的是，没有发现预计会截断该蛋白质的突变。与之前的研究相结合，本文报告的结果表明，种系或体细胞 DICER1 突变在 TGCT 病因中的作用非常有限。
The RNase III enzyme DICER1 plays a central role in maturation of microRNAs. Identification of neoplasia-associated germ-line and somatic mutations in DICER1 indicates that mis-expression of miRNAs in cancer may result from defects in their processing. As part of a recent study of DICER1 RNase III domains in 96 testicular germ cell tumors, a single RNase IIIb domain mutation was identified in a seminoma. To further explore the importance of DICER1 mutations in the etiology of testicular germ cell tumors (TGCT), we studied germ-line DNA samples from 43 probands diagnosed with familial TGCT. We carried out High Resolution Melting Curve Analysis of DICER1 exons 2–12, 14–19, 21 and 24–27. All questionable melt curves were subjected to confirmatory Sanger sequencing. Sanger sequencing was used for exons 13, 20, 22 and 23. Intron-exon boundaries were included in all analyses. We identified 12 previously reported single nucleotide polymorphisms and two novel single nucleotide variants. No likely deleterious variants were identified; notably no mutations that were predicted to truncate the protein were identified. Taken together with previous studies, the findings reported here suggest a very limited role for either germ-line or somatic DICER1 mutations in the etiology of TGCT.