Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer.
Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer.
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DOI：
10.1038/srep37984
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发表时间：
2017-01-04
影响因子：
4.6
通讯作者：
Lázaro C
中科院分区：
文献类型：
--
作者：
Feliubadaló L;Tonda R;Gausachs M;Trotta JR;Castellanos E;López-Doriga A;Teulé À;Tornero E;Del Valle J;Gel B;Gut M;Pineda M;González S;Menéndez M;Navarro M;Capellá G;Gut I;Serra E;Brunet J;Beltran S;Lázaro C
下一代测序面板已开发用于遗传性癌症，尽管与外显子组测序相比，其成本效益存在一些争议。将两组的性能与外显子组测序进行比较。选择了24名患者：10名具有确定的突变（对照组）和14名疑似遗传性癌症但没有突变（发现组）。TruSight癌症（94个基因）和定制面板（122个基因）与外显子组测序一起评估。两个组和外显子组测序靶向83个基因。超过99%的碱基在面板中具有超过30倍的读取深度，而外显子组测序覆盖了94%。使用TruSight Cancer，采用标准设置的变体调用鉴定了对照组中的10个突变，但MSH6 c.255dupC除外。在发现集中，在该组基因中鉴定了240种独特的非沉默编码和规范剪接位点变体，其中7种为脓毒症致病性（ATM、BARD 1、CHEK 2、ERCC 3、FANCL、FANCM、MSH 2）。这三种方法在共享基因中发现了相似数量的变体。外显子组比面板更昂贵，但提供了额外的数据。就成本和深度而言，面板是遗传诊断的合适选择，尽管外显子组也可以识别非靶向基因中的变体。
Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eighty-three genes were targeted by the two panels and exome sequencing. More than 99% of bases had a read depth of over 30x in the panels, whereas exome sequencing covered 94%. Variant calling with standard settings identified the 10 mutations in the control set, with the exception of MSH6 c.255dupC using TruSight Cancer. In the discovery set, 240 unique non-silent coding and canonic splice-site variants were identified in the panel genes, 7 of them putatively pathogenic (in ATM, BARD1, CHEK2, ERCC3, FANCL, FANCM, MSH2). The three approaches identified a similar number of variants in the shared genes. Exomes were more expensive than panels but provided additional data. In terms of cost and depth, panels are a suitable option for genetic diagnostics, although exomes also identify variants in non-targeted genes.
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DOI：
10.1038/gim.2014.40
发表时间：
2014-11
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
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DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
5.8
作者：
Li, Heng
通讯作者：
Li, Heng
DOI：
10.1158/1078-0432.ccr-13-2287
发表时间：
2014-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Pennington KP;Walsh T;Harrell MI;Lee MK;Pennil CC;Rendi MH;Thornton A;Norquist BM;Casadei S;Nord AS;Agnew KJ;Pritchard CC;Scroggins S;Garcia RL;King MC;Swisher EM
通讯作者：
Swisher EM