ABSTRACT
Cervical carcinoma is etiologically associated with the human papilloma virus (HPV), HPV 16 and HPV 18 being the most common. Viral DNA is thought to persist mostly in the episomal form in early tumor development, and in the integrated form in carcinomas. This assumption was checked with a new method that discriminated between RNAs transcribed from episomal and integrated HPV DNAs. Both forms were detected in carcinomas of Russian patients regardless of the disease stage. The data were verified by two other methods. RNA with sequences of the HPV transforming gene E7 proved to be transcribed from either DNA form. The results suggest that HPV integration is not crucial for carcinoma progression.
Subject(s)
DNA, Viral/analysis , DNA-Binding Proteins , Papillomaviridae/genetics , Uterine Cervical Neoplasms/chemistry , Female , Humans , Oncogene Proteins, Viral/genetics , Papillomaviridae/physiology , Reverse Transcriptase Polymerase Chain Reaction , Virus IntegrationABSTRACT
Chromosome 6 is frequently affected in different tumors. However, little information exists on chromosome 6 deletions in cervical cancer. We have studied loss of heterozygosity (LOH) and microsatellite instability (MIN) in 62 invasive squamous cell carcinomas of the cervix (CC) using 19 polymorphic microsatellite markers spanning both arms of chromosome 6 and one marker located at 5p15. We found that LOH at chromosome 6 is a common feature of cervical carcinomas: 90% (56/62) of CC had LOH at least at one locus and about 58% (36/62) had LOH on both arms of chromosome 6. The highest LOH incidence was shown in HLA region (6p21.3-6p21.1) with markers D6S273 and D6S276 in 52.7% and 45.2% of informative cases respectively. Frequent LOH on 6q was found at loci D6S311 (6q24-25. 1), D6S305 (6q26) and D6S281 (6q27-6qter) in 37.8%, 33.3% and 39.0% of informative cases respectively. There was no significant correlation observed between clinical parameters of cervical cancer (age, histologic grade, clinical stages and progression) and LOH frequency. Microsatellite instability was found in 3 out of 62 cases (4.8%) at three and more loci out of 20 tested. The study shows that several regions on 6p and 6q may harbour potential tumor-suppressor genes important for cervical cancer progression.