1. Materials & Methods References Introduction 1.Kim TH, Jeon YJ, Kim WY, Kim HS: HESAS: HERVs expression and structure analysis system. Bioinformatics 2005, 15:1699-1970. 2. Kim DS, Kim TH, Huh JW, Kim IC, Kim SW, Park HS, Kim HS : LINE FUSION GENES: a database of LINE expression in human genes. BMC Genomic 2006, 7:139 Min-In Bae 1, Yun-Ji Kim 1, Jae-Won Huh 1, Dae-Soo Kim 2, Sung-Jin Jang 1, and Heui-Soo Kim 1, 2 1Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea 2 PBBRC, Interdisciplinary Research Program of Bioinformatics, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea http://www.primate.or.kr Identification of fusion transcripts with retroviral elements in relation to cancers The human genome is estimated to be composed of 45% transposable elements (TEs). They have been reported to have capacity for affecting adjacent genes by altering transcriptional regulation. Most TEs are transcriptionally silent in normal tissues. However, TEs have been found to be expressed specifically in cancer cell lines. Here we investigated the cancer specific fusion transcript with TEs using bioinformatics and experimental approaches. To identify the candidate cancer markers, we adopted an analysis pipeline for screening methods to detect cancer- specific expression from expressed human sequences and developed a database. Total 999 genes fused with transposable elements were found to be cancer-specific in our analysis of the EST database. To confirm the candidate marker transcripts, experimental validation was conducted by RT-PCR analysis in tumor/adjacent normal tissues and corresponding cancer cell lines. Our results could contribute greatly to understand the human cancers in relation to transposable element. Abstract Pseudogenes LTR provirus LTR Enodgenous retrovirus Exogenous Retroviruses Retrotransposons Endogenous Retroviruses budding proteins (gag, env) translation infection REVERSE TRANSCRIPTION transcription integration cDNA AAA mRNA AAA transcription LTR re - integration translation proteins (gag, env) REVERSE TRANSCRIPTION cDNA Particle formation(budding) LTR re - integration Particle formation no re-infection LTR retrotransposon AAA transcription mRNA cDNA REVERSE TRANSCRIPTION Cellular gene pseudogene splicing AAA REVERSE TRANSCRIPTION cDNA integration transcription spliced- mRNA translation proteins (gag) Hypothetical model for retroelements in human genome Promoter region 1 exon Transcription change Supplying the Promoter or Enhancer 1 exon 2 exon Exonization in UTR and CDS region Alternative Promoter 1 exon 2 exon Alternative Polyadenylation last exon Results & Discussion 11% 82% 6% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 5 ′ UTRCDS3 ′ UTR Location of transposable elements fusion EST Percent of exons % Chr.12 q24.31 NM_004276.3 BG470119 NM_001033677.1 NM_031205.2 AluJo/FRAM Coding regionUntranslated region (calcium binding protein 1 isoform) CABP1 Materials & Methods DATABASE Experimental Approach (ATP-binding cassette, sub-family D (ALD), member 4) ABCD4 NM_020323.1 NM_0020324.1 NM_020326.2 NM_020325.1 NM_005050.1 BM817791 AluJo/FRAM Coding region Untranslated region q24.3 Chr.14 399 bp 237 bp M 1 2 3 4 5 6 7 M 1 2 3 4 NO. Sample cDNA 1 normal colon 2 tumor colon 3 normal colon 4HT29 5COLO201 6COLO205 7HCT116 NO.Sample cDNA 1normal stomach 2tumor stomach 3normal stomach 4AZ521 Bioiformatics Experiments Tumor / normal tissues & Cancer cell-lines RT-PCR