Heyn Holger
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
PLoS Genet. 2016 Mar 3;12(3):e1005826. doi: 10.1371/journal.pgen.1005826. eCollection 2016 Mar.
The interpretation of noncoding alterations in cancer genomes presents an unresolved problem in cancer studies. While the impact of somatic variations in protein-coding regions is widely accepted, noncoding aberrations are mostly considered as passenger events. However, with the advance of genome-wide profiling strategies, alterations outside the coding context entered the focus, and multiple examples highlight the role of gene deregulation as cancer-driving events. This review describes the implication of noncoding alterations in oncogenesis and provides a theoretical framework for the identification of causal somatic variants using quantitative trait loci (QTL) analysis. Assuming that functional noncoding alterations affect quantifiable regulatory processes, somatic QTL studies constitute a valuable strategy to pinpoint cancer gene deregulation. Eventually, the comprehensive identification and interpretation of coding and noncoding alterations will guide our future understanding of cancer biology.
癌症基因组中非编码改变的解释是癌症研究中一个尚未解决的问题。虽然蛋白质编码区域体细胞变异的影响已被广泛接受，但非编码畸变大多被视为过客事件。然而，随着全基因组分析策略的发展，编码区域以外的改变成为焦点，多个实例凸显了基因失调作为癌症驱动事件的作用。本综述描述了非编码改变在肿瘤发生中的意义，并提供了一个理论框架，用于通过数量性状位点（QTL）分析来识别因果体细胞变异。假设功能性非编码改变会影响可量化的调控过程，体细胞QTL研究是确定癌症基因失调的一项有价值的策略。最终，对编码和非编码改变的全面识别和解释将引领我们未来对癌症生物学的理解。
