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Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions

Oncogene volume 21, pages 419–426 (2002)Cite this article

Abstract

Persistent high risk type human papillomavirus (HR–HPVs) infections induce dysplasia or cancer of the anogenital tract, most notably of the uterine cervix. The viral genome usually persists and replicates as an episomal molecule in early dysplasia, whereas in advanced dysplasia or cervical cancer HPV genomes are frequently integrated into the chromosomal DNA of the host cell. Previous studies suggested that modification of critical cellular sequences by integration of HPV genomes might significantly contribute to the neoplastic transformation of anogenital epithelia (insertional mutagenesis). This prompted us to characterize the integration loci of high risk HPV genomes in a large set of genital lesions. We amplified E6/E7 oncogene transcripts derived from integrated HPV16 and HPV18 genomes and characterized in detail the co-transcribed cellular sequences of 64 primary genital lesions and five cervical cancer cell lines. Database analyses of the cellular parts of these fusion transcripts revealed 51 different integration loci, including 26 transcribed genes (14 known genes, 12 EST sequences with unknown gene function). Seventeen sequences showed similarity to repetitive elements, and 26 sequences did not show any database match other than genomic sequence. Chromosomal integration loci were distributed over almost all human chromosomes. Although we found HPV sequences integrated into cancer related genes and close to fragile sites, no preferential site or integration motif could be identified. These data demonstrate that target directed insertional mutagenesis might occur in few HPV-induced anogenital lesions, however, it is rather the exception than the rule.

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Author notes

  1. Ruediger Ridder

    Present address: MTM Laboratories AG, Heidelberg, 69120, Germany

  2. Ruediger Klaes

    Present address: Institute of Human Genetics, University of Heidelberg, Germany

  3. Nicolas Wentzensen and Ruediger Ridder: These authors contributed equally to this paper

Authors and Affiliations

  1. Division of Molecular Pathology, Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany

    Nicolas Wentzensen, Ruediger Klaes, Svetlana Vinokurova, Ulrike Schaefer & Magnus von Knebel Doeberitz

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  1. Nicolas Wentzensen
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  2. Ruediger Ridder
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  6. Magnus von Knebel Doeberitz
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Correspondence to Magnus von Knebel Doeberitz.

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Wentzensen, N., Ridder, R., Klaes, R. et al. Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions. Oncogene 21, 419–426 (2002). https://doi.org/10.1038/sj.onc.1205104

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