Bearfoot Jennifer L, Choong David Y H, Gorringe Kylie L, Campbell Ian G
VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Clin Cancer Res. 2008 Nov 15;14(22):7246-50. doi: 10.1158/1078-0432.CCR-08-1348.
There is accumulating evidence that microRNAs may function like classic tumor suppressor genes but little is known about their mechanism of inactivation in cancer cells. We investigated whether somatic mutations are a common mechanism of inactivation of microRNA genes in ovarian cancer.
Ten cancer-implicated microRNA genes were analyzed for somatic mutations in 90 ovarian epithelial cancers and matching normal DNA. High-resolution melt analysis and bidirectional sequencing was used to detect sequence variations.
High-resolution melt analysis and direct sequencing did not identify any somatic mutations but did reveal numerous novel and previously reported germ line base substitutions, deletions, and insertions surrounding the mature microRNA sequences. The majority of variants were detected in the same proportion of non-cancer control individuals suggesting that they do not represent ovarian cancer-predisposing alleles.
The absence of somatic mutations in any of the 10 cancer-implicated microRNAs in our large cohort of ovarian tumors suggests that this may be an uncommon mechanism of inactivation of microRNAs in ovarian cancer.
越来越多的证据表明，微小RNA可能具有与经典肿瘤抑制基因类似的功能，但对于它们在癌细胞中的失活机制却知之甚少。我们研究了体细胞突变是否是卵巢癌中微小RNA基因失活的常见机制。
对90例卵巢上皮癌及配对的正常DNA中的10个与癌症相关的微小RNA基因进行体细胞突变分析。采用高分辨率熔解分析和双向测序检测序列变异。
高分辨率熔解分析和直接测序未发现任何体细胞突变，但确实揭示了成熟微小RNA序列周围大量新的和先前报道的种系碱基替换、缺失和插入。大多数变异在非癌对照个体中以相同比例被检测到，这表明它们不代表卵巢癌易感等位基因。
在我们的大型卵巢肿瘤队列中，10个与癌症相关的微小RNA中均未检测到体细胞突变，这表明这可能是卵巢癌中微小RNA失活的一种不常见机制。
