Carcinogenesis Advance Access originally published online on August 27, 2007
Carcinogenesis 2007 28(12):2484-2490; 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
* To whom correspondence should be addressed. Fax: +86 27 68756253; Email: rjzhou{at}whu.edu.cn Correspondence may also be addressed to Hanhua Cheng. Tel: +86 27 87889294; Fax: +86 27 68756253;Email: hhcheng{at}whu.edu.cn
Alternative pre-messenger RNA (mRNA) splicing is a key molecular event that allows for protein diversity and plays important roles in development and disease. Alternative pre-mRNA splicing regulations during spermatogenesis and alternative pre-mRNA splicing etiology in testicular tumorigenesis are yet to be characterized. By genome-wide analysis, here we describe alternative splicing features that distinguish distinctive patterns of alternative pre-mRNA splicing 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. Reverse transcription–polymerase chain reaction confirmed that most of these transcript candidates from mouse testis were testis specific. Around 40% of the transcripts were from unknown/hypothetical genes, which were useful for further functional analysis. These transcripts were not overlapped, indicating lack of evolutionary conservation. Further chromosome mapping showed distinct chromosomal preference of alternative pre-mRNA splicing events. Comparison analysis indicated that alternative pre-mRNA splicing 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 alternative pre-mRNA splicing 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.
Abbreviations: EST, expressed sequence tag; mRNA, messenger RNA; PCR, polymerase chain reaction; RT, reverse transcription
Received May 7, 2007; revised July 30, 2007; accepted August 14, 2007.