title: Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites.
abstract: The development of cervical cancer is highly associated with human papillomavirus (HPV) infection. HPV integration into the genome of infected cervical cells is temporally associated with the acquisition of the malignant phenotype. A relationship between the sites of HPV integration in cervical cancer and the position of the common fragile sites (CFSs) has been observed at the cytogenetic level. To explore this relationship at the molecular level, we used a PCR-based method to rapidly isolate cellular sequences flanking the sites of HPV16 integrations in primary cervical tumors. Human bacterial artificial chromosome clones were isolated based on these flanking sequences and used as probes for fluorescence in situ hybridization on metaphases derived from cells cultured in the presence of aphidicolin. Our data demonstrate that HPV16 integrations in cervical tumors frequently occur within CFSs at the molecular level. In addition, we have determined the precise molecular locations of the CFSs FRA6C and FRA17B.
authors.affiliation: Department of Biochemistry, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Thorland
authors.forename: S L
authors.initials: SL
authors.lastname: Myers
authors.forename: D H
authors.initials: DH
authors.lastname: Persing
authors.forename: G
authors.initials: G
authors.lastname: Sarkar
authors.forename: R M
authors.initials: RM
authors.lastname: McGovern
authors.forename: B S
authors.initials: BS
authors.lastname: Gostout
authors.forename: D I
authors.initials: DI
authors.lastname: Smith
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology*; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D002877:Chromosomes, Human / Q000235:genetics; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics*; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000821:virology*; D016662:Virus Integration / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004279:DNA, Viral