Genomic integration of oncogenic HPV and gain of the human telomerase geneTERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer
| Autor: | Frans C. S. Ramaekers, L E Morrison, Frank Smedts, Miriam A.F. Kamps, Wendy Theelen, Pascal P. H. Hommelberg, E.J.M. Speel, CS Herrington, Anton H. N. Hopman |
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| Rok vydání: | 2006 |
| Předmět: |
Candidate gene
Pathology medicine.medical_specialty Centromere Uterine Cervical Neoplasms Cervix Uteri Biology Cervical intraepithelial neoplasia medicine.disease_cause Pathology and Forensic Medicine Telomerase RNA component Uterine Cervical Dysplasia medicine Humans Neoplasm Invasiveness Papillomaviridae Telomerase In Situ Hybridization Fluorescence Chromosome Aberrations Cervical cancer Ploidies medicine.diagnostic_test Gene Amplification DNA Neoplasm medicine.disease Cell Transformation Neoplastic Dysplasia Cancer research RNA Female Chromosomes Human Pair 3 Carcinogenesis Chromosomes Human Pair 7 Fluorescence in situ hybridization |
| Zdroj: | The Journal of Pathology. 210:412-419 |
| ISSN: | 1096-9896 0022-3417 |
| DOI: | 10.1002/path.2070 |
| Popis: | Recently proposed events associated with the progression of cervical intraepithelial neoplasia (CIN) 2/3 to cervical carcinoma include integration of human papillomavirus (HPV) into the host genome, genomic instability, and an increase in chromosome 3q copy number. In particular, the gene coding for the RNA component of telomerase (TERC) at 3q26 has been implicated as a possible candidate gene. Since it is not known to date how these events are temporally related during cervical carcinogenesis, the aim of the present study was to assess the correlation between TERC gene copy number and the physical status of HPV during progression in cervical neoplasia. Solitary precursor lesions of the uterine cervix (CIN 2/3, n = 17), lesions associated with a micro-invasive carcinoma (CIN 3&mCA, n = 13), and advanced invasive carcinomas (invCA, n = 7) were analysed by fluorescence in situ hybridization (FISH) to determine the physical status of the virus and TERC gene copy number. The TERC gene was increasingly gained with progression of CIN 2/3 (3 of 17) through CIN 3&mCA (7 of 13) to invCA (5 of 7). In the lesions exhibiting gain of TERC, the virus was predominantly integrated. This was seen in eight of ten diploid lesions, indicating that these events can occur prior to aneuploidization and are strongly associated with the progression of CIN 3 to mCA and invCA (p < 0.001). With progression to carcinoma, a number of these lesions show polyploidization, resulting in aneuploidy and high TERC gene copy numbers. In conclusion, genomic integration of oncogenic HPV and gain of the human telomerase gene TERC appear to be important associated genetic events in the progression of uterine cervical dysplasia to invasive cancer. |
| Databáze: | OpenAIRE |
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