Integration of human papillomavirus type 6a DNA in a tonsillar carcinoma: chromosomal localization and nucleotide sequence of the genomic target region.

ABSTRACT

Human papillomavirus type 6a (HPV 6a) DNA was detected in a tonsillar carcinoma both as integrated and episomal molecules, and one viral-cellular junction was molecularly cloned (Bercovich et al., J. Gen Virol., 72 2569-2572, 1991). The cellular sequence was used as a probe for the isolation of a cosmid from a normal human genomic DNA library. A 2.7-kilobase subclone including the integration site was sequenced. It was shown to contain sequences with similarities to the E2 and L2 regions of human papillomaviruses, a 5' truncated long interspersed repeated DNA element type 1 retrotransposon, and a fragment of an O-repeat element. The chromosomal localization of the integration site was determined to be at region 24 of the long arm of chromosome 10 (10q24). This is the region where the fragile site is located in which HPV 18 DNA is integrated in the cell line FEP18-5. In addition it contains the site of breakpoints affecting protooncogenes Hox11 and Lyt10. Other genes related to cell division and DNA repair have also been mapped to this chromosomal band. Analysis of genomic DNA of cell lines and patients using 10q24-derived probes is presented. The integration of human papillomavirus type 6 DNA into chromosome 10q24 may have disrupted a cellular gene critical for normal cell growth, which further analysis should help to identify.