Shallow whole genome sequencing for robust copy number profiling of formalin-fixed paraffin-embedded breast cancers
Shallow whole genome sequencing for robust copy number profiling of formalin-fixed paraffin-embedded breast cancers
复制标题
DOI：
10.1016/j.yexmp.2018.03.006
复制
发表时间：
2018-06-01
影响因子：
3.6
通讯作者：
Caldas, Carlos
中科院分区：
文献类型：
--
作者：
Chin, Suet-Feung;Santonja, Angela;Caldas, Carlos
具有相关临床数据的病理学档案是转化研究的宝贵资源，但大多数癌症样本都是福尔马林固定石蜡包埋（FFPE）组织。因此，FFPE组织是基因组谱研究的重要资源，但由于提取的核酸的量和质量低而未得到充分利用。我们通过浅层全基因组测序分析了356例乳腺癌患者使用DNA提取的FFPE组织的拷贝数景观。我们从2个试剂盒中共生成了491个测序文库，从98.4%的文库中获得了数据，其中86.4%的文库质量良好。我们从低至3.8 ng的输入DNA生成文库，并发现成功与输入DNA的量和质量、加工位点和固定组织的年龄无关。由于拷贝数改变（CNA）在乳腺癌中起着重要作用，因此我们必须能够使用FFPE档案，并且我们在本研究中已经证明sWGS是进行此类分析的可靠方法。
Pathology archives with linked clinical data are an invaluable resource for translational research, with the limitation that most cancer samples are formalin-fixed paraffin-embedded (FFPE) tissues. Therefore, FFPE tissues are an important resource for genomic profiling studies but are under-utilised due to the low amount and quality of extracted nucleic acids. We profiled the copy number landscape of 356 breast cancer patients using DNA extracted FFPE tissues by shallow whole genome sequencing. We generated a total of 491 sequencing libraries from 2 kits and obtained data from 98.4% of libraries with 86.4% being of good quality. We generated libraries from as low as 3.8 ng of input DNA and found that the success was independent of input DNA amount and quality, processing site and age of the fixed tissues. Since copy number alterations (CNA) play a major role in breast cancer, it is imperative that we are able to use FFPE archives and we have shown in this study that sWGS is a robust method to do such profiling.