To DNA or not to DNA? That Is the Question, When It Comes to Molecular Subtyping for the Clinic!
To DNA or not to DNA? That Is the Question, When It Comes to Molecular Subtyping for the Clinic!
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DOI：
10.1158/1078-0432.ccr-11-0462
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发表时间：
2011-08-01
影响因子：
11.5
通讯作者：
Ylstra, Bauke
中科院分区：
文献类型：
--
作者：
Smeets, Serge J.;Harjes, Ulrike;Ylstra, Bauke
全基因组RNA表达谱已经产生了对多种癌症具有强预测或预后价值的肿瘤亚型。最近，对于乳腺癌，两种RNA表达分类器已被世界卫生组织（WHO）采用并被食品和药物管理局（FDA）批准。此外，基于DNA拷贝数谱，已经描述了具有不同预后的肿瘤亚型，但尚未导致临床实施。由下一代DNA样品测序引起的基因组革命同时呈现额外的突变、平衡易位、单核苷酸多态性（SNP）和拷贝中性杂合性丢失数据。我们预计，当这些多维度的DNA因素被实施时，DNA分析在临床上的潜力将进一步提高。在这里，我们用DNA拷贝数来评估当前的分层能力。在使用400个已发表的乳腺癌样本数据的训练和验证方法中，我们表明DNA拷贝数分类器可以准确地对RNA表达亚型进行分类。我们认为这是使用DNA进行基因组分型的临床实施的重要一步，并讨论了即将到来的技术将给DNA调色板带来的额外维度。临床癌症研究; 17（15）; 4959-64。（C）2011年《非洲标准化评论》。
Genome-wide RNA expression profiling has yielded tumor subtypes with strong predictive or prognostic value for a wide variety of cancers. Recently, for breast cancer two RNA expression classifiers have been adopted by the World Health Organization (WHO) and approved by the Food and Drug Administration (FDA). Also on the basis of DNA copy number profiles, tumor subtypes with different prognosis have been described, but have not yet led to clinical implementation. The genomic revolution caused by next generation sequencing of DNA samples presents additional mutation, balanced translocations, single-nucleotide polymorphisms (SNP), and copy neutral loss of heterozygosity data simultaneously. We foresee a further boost of the potential of DNA profiling in the clinic when these multidimensional DNA factors will be implemented. Here we evaluate the current stratification power with DNA copy numbers. In a training and validation approach using data of 400 published breast cancer samples, we show that a DNA copy number classifier accurately classifies RNA expression subtypes. We consider this an important step forward for clinical implementation of genomic subtyping using DNA and discuss the extra dimensions upcoming techniques will bring to the DNA palette. Clin Cancer Res; 17(15); 4959-64. (C)2011 AACR.