Human Papillomavirus Type 18 Integration Site 2

The DNA of human papillomavirus (HPV) types 16 and 18 has been found closely associated with human genital cancers, supporting an etiologic role for these viruses. Both HPV16 and HPV18 DNA sequences have also been detected in cell lines derived from cervical cancer. For example, the most famous such line, HeLa, contains HPV18 DNA amplified about 10- to 50-fold together with the flanking cellular sequences. Most, if not all, HPV-positive mRNAs from HeLa are virus-cell fusion transcripts. The host cell sequences are spliced to the 5-prime HPV18 exons. In a primary cervical carcinoma, Durst et al. (1987) found that HPV-16 flanking sequences were localized to chromosome regions 20pter-q13 and 3p25-qter, regions that also contain the protooncogenes SRC (190090) and RAF1 (164760), respectively. In the SiHa cervical carcinoma-derived cell line, Durst et al. (1987) demonstrated that the HPV16 integration site was into chromosome region 13q14-q32. The HPV18 integration site in SW756 cervical carcinoma cells was in chromosome 12 but was not closely linked to the KRAS2 gene (190070). In 2 cervical carcinoma cell lines, HeLa and C4-I, HPV18 DNA was integrated in chromosome 8, 5-prime to the MYC gene (190080). All this suggested that at least in some genital tumors, cis-activation of cellular oncogenes by HPV may be involved in malignant transformation of cervical cells. Popescu et al. (1987) also found that the HPV18 DNA in the cervical carcinoma cell line SW756 was integrated at a single site, namely, 12q13. Multiple copies were present at this site, which was determined by in situ hybridization. The single integration site corresponds to a heritable fragile site which, Popescu et al. (1987) suggested, may have facilitated the integration of the viral DNA.