Cytogenetics and cytology of retinoblastomas
| Authors | |
|---|---|
| Year of publication | 2003 |
| Type | Article in Periodical |
| Magazine / Source | J Cancer Res. Clin.Oncol. |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | retinoblastoma; Numerical aberrations; Nuclear topography; Apoptosis |
| Description | Using the repeated FISH technique, the average distances between the nuclear membrane and the fluorescence gravity centre (FGC) of seven selected chromosomes were determined in the same tumour population and three other cell types. Chromosome order in positioning from the nuclear membrane was similar in all cell populations investigated. Our experimental studies were focused on specific genetic loci relevant for retinoblastoma tumour pathogenesis. We revealed a certain heterogeneity in the copy number of the Rb1, N-myc and TP53 gene loci in tumour cells. In addition, in lymphocytes isolated from peripheral blood of the patients, a high degree of copy number heterogeneity was also detected. In 60 % of analysed retinoblastomas we observed numerical aberration involving the centromeric region of chromosome 6. In these tumours, apoptotic bodies were found irrespective of clinical therapy. Chromosome instability seems to be a typical feature of primary retinoblastomas as well as of the human pseudodiploid cell line Y79. These cells of a hereditary form of retinoblastoma (Y79) were irradiated by gamma rays and exposed to anti-tumour drugs such as etoposide, vincristine and cisplatin. These treatments induced apoptosis, changes in the cell cycle profile and specific modifications in the nuclear topography of selected loci. Treatment with a non-lethal concentration of hydroxyurea was shown to induce the loss of the amplified N-myc gene involved in the homogenously staining region (HSR) that was found to be associated with the nuclear membrane of retinoblastoma Y79 cells. |
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