Complex genomic rearrangement within the 12q15 multiple aberration region induced by integrated human papillomavirus 18 in a cervical carcinoma cell line.
Human papillomavirus (HPV) DNA is integrated into the host genome in cervical cancer. The cervical carcinoma cell line SW756 has integrated HPV-18 DNA in chromosome region 12q15, in the papillomavirus-associated locus-2 (PAL2). By polymerase chain reaction and hybridization of an arrayed cosmid library with oligonucleotides from the rearranged allele, we determined the pre-integration germline structure of the region. PAL2 was located approximately 10 kb from sequence-tagged site marker U27131, which was the marker most proximal to the 3' flank of the integrated viral DNA. HPV-18 DNA integration induced a complex genomic rearrangement resulting in inversion and deletion of cellular sequences. PAL2 is within the multiple aberration region, which has been shown to be affected in several types of benign tumors of mesenchymal origin. The integrated viral DNA was located 50 kb from a CpG island and 150 kb upstream of the high-mobility group I-C (HMGI-C) gene. The HMGI-C gene and the integrated HPV-18 DNA had opposite transcriptional orientations. No overexpression or altered message of the HMGI-C gene was detected in three cervical carcinoma cell lines. The integrated viral DNA did not affect any other known gene in the region and may be a marker for an unknown gene associated with malignant tumor phenotypes.
Gallego
M I
MI
Unidad de Genética y Medicina Molecular (Consejo Superior de Investigaciones Científicas), Instituto de Salud Carlos III, Majadahonda, Spain.
Schoenmakers
E F
EF
Van de Ven
W J
WJ
Lazo
P A
PA
D001483:Base Sequence; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D004279:DNA, Viral; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000235:genetics*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D016662:Virus Integration
D004279:DNA, Viral