INTEGRATION OF HUMAN PAPILLOMAVIRUS TYPE 6A DNA IN A TONSILLAR CARCINOMA - CHROMOSOMAL LOCALIZATION AND NUCLEOTIDE-SEQUENCE OF THE GENOMIC TARGET REGION

Human papillomavirus type 6a (HPV 6a) DNA was detected in a tonsillar carcinoma both as integrated and episomal molecules, and one viral-cel lular junction was molecularly cloned (Bercovich et at, J. Gen Virol., 72: 2569-2572, 1991). The cellular sequence was used as a probe for t he isolation of a cosmid from a normal human genomic DNA library. A 2. 7-kilobase subclone including the integration site was sequenced. It w as shown to contain sequences with similarities to the E2 and L2 regio ns of human papillomaviruses, a 5' truncated long interspersed repeate d DNA element type 1 retrotransposon, and a fragment of an O-repeat el ement. The chromosomal localization of the integration site was determ ined 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 i s integrated in the cell line FEP18-5. In addition it contains the sit e 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 papi llomavirus type 6 DNA into chromosome 10q24 may have disrupted a cellu lar gene critical for normal cell growth, which further analysis shoul d help to identify.