Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20037, USA.
McCormick Genomics and Proteomics Center, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20037, USA.
Sci Rep. 2017 Aug 15;7(1):8287. doi: 10.1038/s41598-017-08416-w.
Asymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent allele-specific overexpression of variants in tumor-suppressor genes. We also report a list of over-expressed variants from non-CGC genes. Overall, our analysis presents an integrated set of features of somatic allele expression and points to the vast information content of the asymmetric alleles in the cancer transcriptome.
转录组中不对称的等位基因含量可以表明潜在遗传变异的功能和选择性特征。然而，在癌症中，不平衡的等位基因（尤其是来自二倍体基因组区域的等位基因）研究甚少。在这里，我们通过癌症基因组图谱（TCGA）系统地量化和整合了乳腺癌患者相应的 RNA 和 DNA 序列数据中的变异等位基因分数。我们在癌症基因普查（CGC）中已知的与癌症相关的基因中测试了等位基因流行率与功能之间的相关性。我们记录了 CGC 基因和整个数据集的功能变异中显著的等位基因偏向表达。值得注意的是，我们发现肿瘤抑制基因中的变异经常表现出特异性的过表达。我们还报告了来自非 CGC 基因的过表达变异列表。总的来说，我们的分析提出了一套体细胞等位基因表达的综合特征，并指出了癌症转录组中不对称等位基因的巨大信息含量。
