Carcinogenesis Advance Access published online on August 27, 2007
Carcinogenesis, doi:10.1093/carcin/bgm194
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Genome-wide detection of testis- and testicular cancer-specific alternative splicing
Department of Genetics and Center for Developmental Biology, College of Life Sciences, Wuhan University, Wuhan 430072, P. R. China
* Corresponding authors: Professors Rongjia Zhou and Hanhua Cheng, Department of Genetics and Center for Developmental Biology, College of Life Sciences, Wuhan University, Wuhan 430072, P. R. China, Fax: 0086-27-68756253, E-mail: rjzhou{at}whu.edu.cn, hhcheng{at}whu.edu.cn
Alternative pre-mRNA splicing (AS) is a key molecular event that allows for protein diversity and plays important roles in development and disease. AS regulations during spermatogenesis and AS aetiology in testicular tumorigenesis have not yet to be characterized. By genome-wide analysis, here we describe alternative splicing features that distinguish distinctive patterns of AS among human testis, testicular cancer and mouse testis. Through computationally subtractive analysis, we detected 80 testis-specific transcript candidates in human testis, 175 in human testicular cancer and 262 in mouse testis, which were integrated into a database. RT-PCR confirmed that the most of these transcript candidates from mouse testis were testis-specific. Around 40% of the transcripts were from unknown/hypothetical genes, which were useful to further functional analysis. These transcripts were not overlapped, indicating lack of evolutionary conservation. Further chromosome mapping showed distinct chromosomal preference of AS events. Comparison analysis indicated that AS in human testicular tumor shared some characters/trends with those in mouse testis. Moreover, human testicular tumor tended to use rare splice-sites and there were also distinct sequences adjacent dominant splice-sites between normal testis and testicular tumor. These special features of AS in human testicular tumor suggested that testicular tumorigenesis was involved in multiple steps/levels of alternative splicing events. Using alternative splicing as a potential source for new clinical diagnostic, prognostic, and therapeutic strategies for treatment of testicular tumors seems to have a bright prospect.
Key Words: testicular tumors alternative splicing chromosomal mapping ESTs
Received May 7, 2007; revised July 30, 2007; accepted August 14, 2007.