Telomerase activity in high-grade cervical lesions is associated with allelic imbalance at 6Q14-22.
Our study attempts to establish the relationship between telomerase activity and allelic imbalance (AI) on chromosomes 3p and 6 in high-risk HPV-containing cervical lesions. These chromosomes were implicated previously in telomerase regulation in HPV containing immortalized cells and cervical cancer cells. Allelotyping and telomerase analysis were carried out on 28 high-grade cervical lesions (CIN III: n = 20; cervical carcinomas: n = 8), using 23 microsatellite markers on 3p, 6p and 6q. Clear telomerase activity was found in 17 of 28 lesions (61%). Allelic imbalance frequency at 6q14-22 was significantly higher in lesions with detectable telomerase activity, compared to lesions without telomerase activity (p = 0.02). No association was found between telomerase activity and AI at any of the remaining regions studied on 3p and chromosome 6. In addition, in telomerase positive passages of the HPV 16 immortalized cell line FK16A, shown recently to be responsive to chromosome 6 mediated telomerase repression, AI was found in the overlapping region of 6q14-27. These data suggest that 6q14-22 may contain 1 or more genes involved in telomerase deregulation and immortalization during cervical carcinogenesis.
Department of Pathology, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Mark
M
van Duin
Renske D M
RD
Steenbergen
Jillian
J
de Wilde
Theo J M
TJ
Helmerhorst
René H M
RH
Verheijen
Elle K J
EK
Risse
Chris J L M
CJ
Meijer
Peter J F
PJ
Snijders
D000328:Adult; D022981:Allelic Imbalance; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D016679:Genome, Viral; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000235:genetics; D010413:Penis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D019098:Telomerase / Q000032:analysis* / Q000235:genetics; D014162:Transfection; D014412:Tumor Virus Infections / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000201:enzymology* / Q000235:genetics
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019098:Telomerase