Identification Of A Indel Mutation In Genes Of Wnt Signaling Pathway In Colorectal Cancers By Next-generation Sequencing And Characterization Of Its Biological Function

TFDP1(Transcription factor Dp-1) is an important transcription factor that is closely associated with cancer of the Wnt/beta-catenin signal pathway. Biology function of TFDP1is binding transcription factor E2F to form heterodimers, and enhance the ability of E2F-DNA binding, activating the transcription of downstream target genes, regulating cell cycle regulation and differentiation. In recent years, malignant tumors researches of the digestive system showed more than90%of colorectal cancer exhibited abnormal activation of the Wnt/beta-catenin signaling pathway. The activation usually accompanied by mutations of the major members of this pathway, such as gene insertion/deletion mutations of APC, beta-catenin and Axin. Researching the gene mutation of Wnt/beta-catenin signaling pathway which impact on the occurrence and development of colorectal cancer is important in detection and treatment of colorectal cancer. However, as a number of transcription factors associated with this signaling pathway, the relationship between the TFDP1’s gene mutation and colorectal cancer still need in-depth study.indel (Insertion-Deletion) means a certain number of nucleotides’ insertion or deletion. Among these indels, single-nucleotide indels are more frequent. Many studies have shown the closely relationship between indels and oncogene. Gene mutation is a popular study direction to research cancer. Over the past years many efforts have been made to learn about the mutational theory of cancer. Next generation sequencing (NGS) technologies have markedly improved sequencing efficiency in the past several years. After successfully implemented of the whole genome mapping, targeted re-sequencing as a quick, cheap, targeted technique will play an important role in the future cancer research. It is necessary to detect genomic regions of related genes including upstream, downstream and intron to study the relationship between the members of the Wnt/beta-cateriin signaling pathway and the pathogenesis of colorectal cancer.In the first part of this paper, we use NimbleGen Sequence Capture technology catching31genes of Wnt/beta-catenin signaling pathway in30pair samples of colorectal cancer and adjacent DNA, then sequencing them with NGS. Ultimately, we identified1110indel mutations which had never been reported. Among them,5indel are localized to exonic regions of genes including the TFDP1(Transcription factor Dp-1) gene.In the second part of this article, we try to find the relationship between the InDel84and the variance of the colorectal cancer cells’ function. Results show that this mutation will increase the speed of cell proliferation. At the same time, the indel84increased cell migration and invasion.