Examples of intragenic HPV16 DNA integration sites.

<p>(A) Tumor T182e has one HPV16 integration site 0182_DJ1, which is transcriptionally active (TA-group 1). The integrated HPV16 DNA is located in the intron (i) between exons (e) 5 and 6 of the cellular gene <i>LIPC</i> (transcript 003, Ensembl ID: ENST00000414170, plus strand, 10 exons), and has the same orientation as <i>LIPC</i>. APOT analysis identified an HPV16-cellular fusion transcript (0182_RJ) in which the viral exon is spliced to the downstream <i>LIPC</i> exon 6. (B) Tumor T892 (TA-group 2) has two HPV16 integration sites (0892_DJ1 and 0892_DJ2), which are both located in the intron between exons 12 and 13 of the cellular gene <i>GPN1</i> (transcript 001, Ensembl ID: ENST00000264718, plus strand, 14 exons). While 0892_DJ1 has the same orientation as <i>GPN1</i>, the transcriptionally active 0892_DJ2 has the opposite orientation. In the transcript 0892_RJ the viral exon is spliced to an alternative cellular exon. (C) In tumor T2319 (TA-group 2), all three identified HPV16 integration sites are located within the cellular gene <i>CASZ1</i> (transcript 003, Ensembl ID: ENST00000377022, 21 exons). Since the <i>CASZ1</i> gene is located on the minus strand, the sense orientation of the gene is from right to left. Junction 2319_DJ1 is located in an intron in opposite direction to <i>CASZ1</i>. Junctions 2319_DJ2 and 2319_DJ3 are located in the terminal exon 21 in the same direction as the <i>CASZ1</i> gene, DJ2 in the terminal part of the translated region and DJ3 in the 3′ untranslated region (3′-UTR). Both are possible templates for the HPV16-cellular fusion transcript 2319_RJ. – In the DJs and RJs, the open boxes denote the HPV16 part and the black boxes/arrows the fused cellular part. The arrow of the DJs indicates the sense orientation of the HPV16 oncogenes. Transcribed DJs and the RJs are shown in red, non-transcribed DJs in blue letters.