Identification of fusion transcripts from chromosomal translocation and ECgene update

Abstract

The main purpose of this study is to identify fusion transcripts caused by chromosomal translocation using transcripts data such as EST and mRNA. We identified 2,074 fusion transcripts candidate with more than two genomic alignments, which are located on different chromosomes and have intact exon length near breakpoints. Analyzing the UTR/CDS of these transcripts on genomic region, we classified them as 3 fusion types. Type Ⅰ is referred as the fusions between a breakpoint located on 5'UTR of gene A and a breakpoint of CDS of gene B, when gene A and gene B is assumed to be fused or on 5'UTR and 5'UTR/CDS. A typical example of type I is a IgH- myc , which the fusion of active promoter region of IgH and coding regions of myc gene lead to overexpression of myc. Once its expression is subjugated by the antibody gene promoters, relentless proliferation of lymphoid cells in which transcriptional promoters are highly active. Type Ⅱ is referred as the fusions between a breakpoint located on coding regions of gene A and a breakpoint of coding regions of gene B, which produce fusion protein when the fusion of CDS and CDS is translated. A well known fusion gene of type Ⅱ is a BCR-ABL, which fusion of two reading frames cause growth promoting signals in a strong, deregulated fashion, and lead to rapid mitosis and inhibition of apoptosis. Type ⅡI is referred as the fusions between a breakpoint located on CDS of gene A and a breakpoint of 3'untranslated region of gene B because the change of 3'UTR may affect RNA regulation such as microRNA targeting, RNA stability and mRNA surveillance. In addition, we examined whether there are change in reading frame after a fusion. Using protein alignment tool, BLASTx, fusion transcripts was aligned to human and mouse proteins of UniProt database. We extracted fusion transcripts with no frame shift and categorized them as type Ⅱ because most of known mRNAs producing fusion protein has no frame shift. We can identify 52 fusion transcripts caused by 5'UTR-CDS fusion, 133 fusion transcripts caused by CDS-CDS, and 545 fusion transcripts caused by CDS-3?UTR fusion, including 122 known mRNAs producing fusion protein(count of fusion genes : 67). It has been reported that fusion genes are specific to tumor subtype. Therefore, this study can contribute to discovery the biomarker for cancer, if we additionally analyze the expression of these fusion genes in tumor cell line. ECgene(http://genome.ewha.ac.kr/ECgene) is genome -based transcript model which was first developed to provide functional annotation for alternatively spliced genes in 2005. For the past two years, ECgene database has been provided on gene prediction track of UCSC genome browser. The ECgene algorithm was applied to nine organisms that include most of the important model organisms. This implies that we have the mRNA model and the subcluster for each splice variant, in addition to the genome-based EST clusters which are equivalent to the UniGene clusters. This update version allows users to access ample annotation tracks in the UCSC genome browser database, thereby facilitating the deduction of functional significance of each splice variant.