title: Two novel unbalanced whole arm translocations are frequently detected in cervical squamous cell carcinoma.
abstract: Chromosomal aberrations are a hallmark of human papillomavirus (HPV)-induced cervical carcinogenesis. The aim of this project was to identify structural chromosomal aberrations which may be characteristic for intraepithelial neoplasias (CIN) and cervical carcinomas (CxCa). Two independent HPV16 immortalized keratinocyte cell lines (HPKIA, HPKII) were used as a cell culture model system for cervical carcinogenesis. Different passages of HPKIA and HPKII were analyzed by multicolor spectral karyotyping. Several chromosomal translocations were identified in HPK cells and were validated by interphase fluorescence in situ hybridization (I-FISH). Three unbalanced whole chromosome arm translocations, der(10;14), der(7;21), and der(7;12), were cell line specific. The presence and frequency of these translocations were then examined by I-FISH in frozen tissue sections from normal cervical epithelia (n=6), CIN2/3 (n=15), and CxCa (n=15). The der(10;14) and der(7;21) were detected in 80% and 53.3% of CIN2/3, and in 60% and 46.7% of CxCa, respectively. The percentage of nuclei with translocations in individual lesions was significantly higher among CxCa. The der(7;12) could only be detected in 27% of CIN2/3. None of the translocations were detected in normal cervical epithelia. The translocated chromosomes may contribute to the clonal expansion of subpopulations in these cases and may thus be of diagnostic relevance.
authors.affiliation: Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Jena, Germany. claudia.backsch@med.uni-jena.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Backsch
authors.forename: Birgit
authors.initials: B
authors.lastname: Pauly
authors.forename: Melanie
authors.initials: M
authors.lastname: Liesenfeld
authors.forename: Cornelia
authors.initials: C
authors.lastname: Scheungraber
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Kristin
authors.initials: K
authors.lastname: Mrasek
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Andreas
authors.initials: A
authors.lastname: Clad
authors.forename: Evelin
authors.initials: E
authors.lastname: Schrock
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Runnebaum
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürst
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology