a global view of cancer-specific transcript variants by subtractive transcriptome-wide analysis全局视图减去transcriptome-wide癌症特异性转录变异的分析.pdfVIP

A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis Chunjiang He, Fang Zhou, Zhixiang Zuo, Hanhua Cheng*, Rongjia Zhou* Department of Genetics and Center for Developmental Biology, College of Life Sciences, Wuhan University, Wuhan, People’s Republic of China Abstract Background: Alternative pre-mRNA splicing (AS) plays a central role in generating complex proteomes and influences development and disease. However, the regulation and etiology of AS in human tumorigenesis is not well understood. Methodology/Principal Findings: A Basic Local Alignment Search Tool database was constructed for the expressed sequence tags (ESTs) from all available databases of human cancer and normal tissues. An insertion or deletion in the alignment of EST/EST was used to identify alternatively spliced transcripts. Alignment of the ESTs with the genomic sequence was further used to confirm AS. Alternatively spliced transcripts in each tissue were then subtractively cross- screened to obtain tissue-specific variants. We systematically identified and characterized cancer/tissue-specific and alternatively spliced variants in the human genome based on a global view. We identified 15,093 cancer-specific variants of 9,989 genes from 27 types of human cancers and 14,376 normal tissue-specific variants of 7,240 genes from 35 normal tissues, which cover the main types of human tumors and normal tissues. Approximately 70% of these transcripts are novel. These data were integrated into a database HCSAS (9/database/human.html, pass. Moreover, we observed that the cancer-specific AS of both oncogenes and tumor suppressor genes are associated with specific cancer types. Cancer shows a preference in the selection