Abstract:
:To obtain a comprehensive overview of chromosomal alterations that may underlie human papillomavirus (HPV)-mediated immortalization, 4 foreskin keratinocyte cell lines generated by transfection with either HPV 16 (cell lines FK16A and FK16B) or HPV 18 (FK18A and FK18B) were subjected to chromosomal analysis using comparative genomic hybridization (CGH). Three cell lines were analyzed both in the mortal state during their extended lifespan and in the subsequent immortal state. From cell line FK18A, only immortal cells were tested. Chromosomal imbalances increased in number through the process of immortalization. Subsequent loss of heterozygosity (LOH) analysis, using a panel of 21 microsatellite markers selected on the basis of CGH losses, revealed no clonal LOHs in cells at the mortal stage. However, in the immortal descendants 67% of underrepresentations detected by CGH were expressed as clonal LOH at the respective loci. Clonal LOHs at 3p, 11p and 13q were detected in 2 cell lines each and were thus considered non-random. Immortal cells of 1 cell line (FK18B) revealed LOH at all 3 loci. Moreover, all immortal cell lines displaying allelic losses at one or more of these loci shared a severely dysplastic phenotype after organotypic culturing, as shown previously. Therefore, loss-of-function mutations of genes at these loci, eventually in combination, are potentially involved in the process of HPV-mediated immortalization that is attended by a loss of terminal differentiation. Since chromosomal changes at these loci are also found in HPV-associated carcinomas in vivo, the HPV-transfected cell lines seem to provide a valuable model system for studying HPV-mediated carcinogenesis.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Steenbergen RD,Hermsen MA,Walboomers JM,Meijer GA,Baak JP,Meijer CJ,Snijders PJdoi
10.1002/(sici)1097-0215(19980504)76:3<412::aid-ijcsubject
Has Abstractpub_date
1998-05-04 00:00:00pages
412-7issue
3eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(19980504)76:3<412::AID-IJCjournal_volume
76pub_type
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