Copy number analysis by low coverage whole genome sequencing using ultra low-input DNA from formalin-fixed paraffin embedded tumor tissue
Copy number analysis by low coverage whole genome sequencing using ultra low-input DNA from formalin-fixed paraffin embedded tumor tissue
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DOI：
10.1186/s13073-016-0375-z
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发表时间：
2016-11-15
期刊：
影响因子：
12.3
通讯作者：
Gorringe, Kylie L.
中科院分区：
文献类型：
--
作者：
Kader, Tanjina;Goode, David L.;Gorringe, Kylie L.
由于产量低且 DNA 降解，从福尔马林固定石蜡包埋 (FFPE) 组织中解锁临床可翻译的基因组信息（包括拷贝数改变 (CNA)）具有挑战性。我们描述了一种稳健、经济高效的低覆盖率全基因组测序 (LC WGS) 方法，使用 5 ng FFPE 衍生的 DNA 进行 CNA 检测。使用 100 ng 或 5 ng 输入 DNA 的 CN 图谱与分子倒置探针 (MIP) 阵列图谱高度一致且具有可比性。 LC WGS 改进了使用 MIP 阵列表现不佳的样品的 CN 谱。我们的技术能够识别档案患者样本中的驱动因素和预后 CNA，以前由于 DNA 限制而被认为不适合进行基因组分析。
Unlocking clinically translatable genomic information, including copy number alterations (CNA), from formalin-fixed paraffin-embedded (FFPE) tissue is challenging due to low yields and degraded DNA. We describe a robust, cost-effective low-coverage whole genome sequencing (LC WGS) method for CNA detection using 5 ng of FFPE-derived DNA. CN profiles using 100 ng or 5 ng input DNA were highly concordant and comparable with molecular inversion probe (MIP) array profiles. LC WGS improved CN profiles of samples that performed poorly using MIP arrays. Our technique enables identification of driver and prognostic CNAs in archival patient samples previously deemed unsuitable for genomic analysis due to DNA limitations.