Large-scale Resequencing Of Target Genomic Regions Involved In Colorectal Cancer For SNPs Detection

The second generation sequencing technology has been widely used in large scale detection of cancer related gene mutations in recent years. Cotorectal cancer is a common malignant tumor and Wnt signal transduction pathway was found to be involved with it. At present, many efforts only took a single gene or the exon genomic regions of the cotorectal related genes into account. Here, we combined NimbleGen sequence capture technology with the second generation sequencing technology, and then developed a comprehensive bioinformatics pipeline,to analyze single nucleotide polymorphism for31colorectal cancer related genes, as well as their upstream, downstream regions.First, we used NimbleGen sequence capture technique to capture the genomic regions of31cotorectal cancer related genes derived from Wnt pathway, including their downstream and upstream regions. Then these regions were sequenced by Solexa sequencing machine and the sequenced short reads were analyzed for SNP site detection. As results,2416SNP sites were detected totally, of which748were new sites. Among these mutations,14were non-synonymous,30synonymous and76occurred in UTR region. Further analysis showed that, in those14non-synonymous mutations, mutation occur in gene MSX2A197T and SNP in TRIM28gene C209F may associate with colorectal cancer; New nonsense mutation chr13:114288328_CT is a terminator gained mutation, may lead to premature termination of transcription of TFDP1gene; The site rs111773256in UTR region was predicted to occur in the interaction site of STK11gene with miR-326/330/330-5p. In the later SNP genotyping step,9out of12SNPs passed the quality control and then were further used for survival time analysis. We found thatrs3106189and rs1052918were related to colorectal cancer survival time when using dominant genetic model. When using additional genetic model, rs3106189was found as well. Our results showed that, the SNP detection and analysis pipeline developed in this work can detect cotorectal cancer related gene mutations, and can be applied to other cancers as wel...