Doctoral theses
Current Record: 2111 of 2436
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| Identifier |
39627 |
| Title |
Μελέτη των γονιδίων ευαισθησίας του ρετινοβλαστώματος Rb-1 και του αναστολέα του κυτταρικού κύκλου Kip1/p27 σε κακοήθειες της παιδικής ηλικίας |
| Alternative Title |
Mutational analysis of the retinoblastoma susceptibility gene and the cell cycle inhibitor Kip1/p27 in pediatric malignancies |
| Creator |
Markaki, Erasmia-Athina M
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| Abstract |
Cancer is considered as a genetic disease that is developed when alterations to molecular pathways which control cell cycle happen. Rb-1 is a tumor suppressor gene encoding for a nuclear phosphoprotein acting as a cell cycle regulator, normally expressed in hematopoietic cells and more often inactivated by point mutations with predominance for exons 20-24. The p27/Kip1 is one of the main cyclin dependent kinase inhibitors. The aim of this study was to correlate the retinoblastoma-1 (Rb-1) and p27/Kip1 gene mutations with the prognosis and progression of childhood acute leukemia and neuroblastoma. Bone marrow slides from 51 children with leukemia (39 acute lymphoblastic leukemia [ALL] and 12 acute myeloid leukemia [AML]) and 9 children with neuroblastoma were studied. Exons 20, 21, 22, 23 and 24 were amplified using the polymerase chain reaction technique. Single strand conformational polymorphism (SSCP) and heterodoublex analysis were performed to detect mutations. Forty one percent of ALL cases and seventy five percent of AML patients had altered conformation in Rb-1 gene. Mutations in Kip1 gene had 50% of T-ALL patients and 25% of AML patients. Half of the children with stage IV neuroblastoma with bone marrow infiltration were found to express altered conformation in exon 22 of Rb-1 gene while none in Kip1. None of the B-ALL had detectable mutations. Ninety percent of high-risk acute leukemias cases exhibited Rb-1 gene mutations. All our cases which did not achieved remission or relapsed, exhibited Rb-1 gene mutations. Rb-1 mutations expressed in the unique standard risk ALL suggest silent or leaky mutation while 90% of ALL cases of median risk with Rb-1 mutations showed more than 20.000 / μl WBC at the onset of the disease. Only thirty three percent of AML that were all the cases with no detectable mutations in either Rb-1 or Kip1, are long-term survivors. The SSCP and heterodoublex analysis showed the same altered conformation for each exon in all cases studied while exon 22 has been considered as the hot spot of the Rb-1 gene. Based upon our results the Rb-1 gene mutations alone or in combination with Kip1/p27 can be used as an independent prognostic factor in acute leukemias in childhood while the mutations of Rb-1 gene only is a finding occurring in advanced stage with bone marrow involvement neuroblastoma.
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| Language |
Greek |
| Issue date |
2003-04-01 |
| Date available |
2003-07-08 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/c/8/0/metadata-dlib-2003markaki.tkl
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| Views |
358 |
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