Exome-wide somatic microsatellite variation is altered in cells with DNA repair deficiencies.
Exome-wide somatic microsatellite variation is altered in cells with DNA repair deficiencies.
复制标题
在具有 DNA 修复缺陷的细胞中，外显子组范围内的体细胞微卫星变异发生了改变。
DOI：
10.1371/journal.pone.0110263
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Garner HR
中科院分区：
文献类型：
--
作者：
Vaksman Z;Fonville NC;Tae H;Garner HR
微卫星（MST）是由1-6个核苷酸组成的串联重复序列，是一种偏向插入和缺失（INDEL）而非单核苷酸多态性（SNPs）的突变热点。大多数MST不稳定性研究仅限于少数位点，即Bethesda标记物，其仅对结肠直肠癌的一个子集提供信息。在本文中，我们评估了下一代测序数据中存在的非单倍型等位基因，以评估DNA修复熟练和DNA修复缺陷细胞系中的体细胞MST变异（SMV）。我们证实，下一代数据中存在的等位基因，不有助于单倍型可以可靠地量化，并用于评估SMV，而不需要匹配的样品进行比较。我们观察到，在没有DNA修复缺陷的DNA修复熟练细胞系MCF 10A、HEK 293和PD 20 RV：D2中发现的SMV模式在样品之间具有一致的模式。此外，我们能够证实，在缺乏功能性BRCA 2、FANCD 2和错配修复的细胞系中SMV模式的变化与受干扰的不同途径一致。使用这种新的外显子组测序分析方法，我们表明，DNA不稳定性可以在样品中识别，并且不稳定性的模式取决于受损的DNA修复机制，并且携带次要等位基因的基因与癌症途径密切相关。用于本研究的MST次要等位基因识别器可在https://github.com/zalmanv/MST_minor_allele_caller上获得。
Microsatellites (MST), tandem repeats of 1–6 nucleotide motifs, are mutational hot-spots with a bias for insertions and deletions (INDELs) rather than single nucleotide polymorphisms (SNPs). The majority of MST instability studies are limited to a small number of loci, the Bethesda markers, which are only informative for a subset of colorectal cancers. In this paper we evaluate non-haplotype alleles present within next-gen sequencing data to evaluate somatic MST variation (SMV) within DNA repair proficient and DNA repair defective cell lines. We confirm that alleles present within next-gen data that do not contribute to the haplotype can be reliably quantified and utilized to evaluate the SMV without requiring comparisons of matched samples. We observed that SMV patterns found in DNA repair proficient cell lines without DNA repair defects, MCF10A, HEK293 and PD20 RV:D2, had consistent patterns among samples. Further, we were able to confirm that changes in SMV patterns in cell lines lacking functional BRCA2, FANCD2 and mismatch repair were consistent with the different pathways perturbed. Using this new exome sequencing analysis approach we show that DNA instability can be identified in a sample and that patterns of instability vary depending on the impaired DNA repair mechanism, and that genes harboring minor alleles are strongly associated with cancer pathways. The MST Minor Allele Caller used for this study is available at https://github.com/zalmanv/MST_minor_allele_caller.
登录
查看更多内容
影响因子：
3.5
作者：
通讯作者：
--
DOI：
10.1073/pnas.95.18.10774
发表时间：
1998-09-01
影响因子：
11.1
作者：
Kruglyak, S;Durrett, RT;Aquadro, CF
通讯作者：
Aquadro, CF
影响因子：
3.3
作者：
Ananda, Guruprasad;Walsh, Erin;Makova, Kateryna D.
通讯作者：
Makova, Kateryna D.
影响因子：
64.5
作者：
Hou, Yong;Song, Luting;Wang, Jun
通讯作者：
Wang, Jun
影响因子：
2.9
作者：
Eckert, KA;Mowery, A;Hile, SE
通讯作者：
Hile, SE