生物
CTCF公司
基因
转录因子
遗传学
调节顺序
癌症研究
突变
抑制器
体细胞
计算生物学
增强子
作者
Husen M. Umer,Marco Cavalli,Michal Dabrowski,Klev Diamanti,Marcin Kruczyk,Gang Pan,Jan Komorowski,Claes Wadelius
摘要
Somatic mutations drive cancer and there are established ways to study those in coding sequences. It has been shown that some regulatory mutations are over-represented in cancer. We develop a new strategy to find putative regulatory mutations based on experimentally established motifs for transcription factors (TFs). In total, we find 1,552 candidate regulatory mutations predicted to significantly reduce binding affinity of many TFs in hepatocellular carcinoma and affecting binding of CTCF also in esophagus, gastric, and pancreatic cancers. Near mutated motifs, there is a significant enrichment of (1) genes mutated in cancer, (2) tumor-suppressor genes, (3) genes in KEGG cancer pathways, and (4) sets of genes previously associated to cancer. Experimental and functional validations support the findings. The strategy can be applied to identify regulatory mutations in any cell type with established TF motifs and will aid identifications of genes contributing to cancer.
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