SNP Arrays in heterogeneous tissue:: Highly accurate collection of both germline and somatic genetic information from unpaired single tumor samples
SNP Arrays in heterogeneous tissue:: Highly accurate collection of both germline and somatic genetic information from unpaired single tumor samples
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DOI：
10.1016/j.ajhg.2008.01.012
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发表时间：
2008-04-01
影响因子：
9.8
通讯作者：
Eng, Charis
中科院分区：
文献类型：
--
作者：
Assie, Guillaume;LaFramboise, Thomas;Eng, Charis
SNP阵列提供可靠的基因型，并能以高分辨率检测染色体畸变。然而，组织异质性是目前对体细胞组织分析的主要限制。我们开发了SOMATICs，这是一个用于准确分析异质组织样本的原始程序。54个样本（42个肿瘤和12个正常组织）通过Illumina Beadarrays处理，然后用SOMATICs分析。我们证明，组织异质性相关的限制不仅可以克服，而且可以转化为优势。首先，正常细胞与肿瘤的混合物可以作为内参，从而可以在没有相应正常组织的情况下高度敏感地检测体细胞缺失。其次，正常细胞的存在可以区分体细胞和种系畸变，并且可以评估组织样本中包含体细胞事件的细胞比例。第三，相对早期和晚期的体细胞事件也可以区分，假设晚期事件只发生在癌细胞的亚群中。最后，正常细胞的混合可以从癌症样本中推断出种系基因型。所有这些信息都可以从任何含有40-75%癌细胞的癌症样本中获得。SOMATICs是一个随时可用的开源程序，它将所有这些功能集成到一个简单的格式中，全面地描述每个染色体事件。
SNP arrays provide reliable genotypes and can detect chromosomal aberrations at a high resolution. However, tissue heterogeneity is currently a major limitation for somatic tissue analysis. We have developed SOMATICs, an original program for accurate analysis of heterogeneous tissue samples. Fifty-four samples (42 tumors and 12 normal tissues) were processed through Illumina Beadarrays and then analyzed with SOMATICs. We demonstrate that tissue heterogeneity-related limitations not only can be overcome but can also be turned into an advantage. First, admixture of normal cells with tumor can be used as an internal reference, thereby enabling highly sensitive detection of somatic deletions without having corresponding normal tissue. Second, the presence of normal cells allows for discrimination of somatic from germline aberrations, and the proportion of cells in the tissue sample that are harboring the somatic events can be assessed. Third, relatively early versus late somatic events can also be distinguished, assuming that late events occur only in subsets of cancer cells. Finally, admixture by normal cells allows inference of germline genotypes from a cancer sample. All this information can be obtained from any cancer sample containing a proportion of 40-75% of cancer cells. SOMATICs is a ready-to-use open-source program that integrates all of these features into a simple format, comprehensively describing each chromosomal event.