SVIBOR - Project code: 3-01-172

MINISTRY OF SCIENCE AND TECHNOLOGY

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Project code: 3-01-172


CYTOGENETIC ANALYSIS IN CHILDREN WITH MALIGNANT DISEASES


Main researcher: PETKOVIĆ, ISKRA (36570)


Assistants
Type of research: applied
Duration from: 04/30/91. to 04/30/99.
Papers on project (total): 57
Papers on project quoted in Current Contents: 6
Institution name: Institut za zaštitu majki i djece, Zagreb (72)
Department/Institute: Pediatric clinic
Address: Klaićeva 16
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)440-455
Fax: 385 (0)451 308
Summary: The results of constitutional C-segment variability, of chromosome instability and acquired chromosome aberrations in children with malignant diseases are presented in this work. The analysis of constitutional karyotype was performed on slides obtained by a routine peripheral blood culture. Malignant cells were analyzed cytogenetically on slides obtained from short-term culture of bone marrow, lymph node or direct method of solid tumor treatment. Morphologic, G- and C-banding methods of chromosome identification was used. An analysis of the C-segment variability of chromosomes 1, 9 and 16 was carried out in 38 children with acute lymphoblastic leukemia and 35 children with solid tumor. This investigation showed significant quantitative variability of C-segment in tested children compared with 90 control subjects. The association of genome instability and malignant cell transformation was investigated in ataxia telangiectasia with malignant lymphoma. Cytogenetic analysis of PHA-stimulated lymphocytes showed chromosomal instability and rearrangement of chromosomes 7 and 14. The analyses of malignant cells revealed pseudodiploid karyotype with structural aberration of chromosomes 1, 5 and 12, but not of chromosomes 7 and 14.These results suggested that malignant cells did not originate by transformation of cells with structural aberration of chromosomes 7 and 14. The study of acquired chromosomal abnormalities in 27 children with ANLL and 55 children with ALL revealed cytogenetic heterogeneity in ANLL and ALL, identified some specific chromosomal aberrations and pointed to the geographic/ethnic differences in the frequency of cytogenetic abnormalities. The prognostic value of cytogenetic findings was detected in 39 patients with acute leukemia. Cytogenetic analysis of malignant cells in children with neuroblastoma and rhabdomyosarcoma showed numerical and structural chromosome aberrations. Of special interest were rare structural rearrangements of chromosomes No.1 and No. 14 in neuroblastoma and premature chromosome condensation in rhabdomyosarcoma. These results contribute to the better understanding of the role of human genom in the process of malignant transformation.

Keywords: Constitutive heterochromatin, chromosome aberrations, malignant diseases in children, acute lymphoblastic leukemia, acute nonlymphocytic leukemia, solid tumors.

Research goals: 1. The aim of the study was to determine the degree of association of cytogenetically evident changes of constitutional karyotype and malignant process in children. This investigation will contribute to the identification of cytogenetic factors related to increased cancer susceptibility in children. 2. The aim of acquired chromosome abnormalities investigation was to determine the frequency, types of clonal chromosome abnormalities and correlation between cytogenetic findings and morphological features and prognosis in our population of children with malignant diseases. This investigation will contribute to the detection of new and rare chromosome aberrations as well as a better understanding of the role of certain chromosome segments in the development of malignant diseses in children.

COOPERATION - PROJECTS


  1. Name of project: 3-01-086 Prognostička vrijednost riziko faktora u liječenju djece s hemoblastozama
    Name of institution: Klinika za dječje bolesti Šalata
    City: 10000 - Zagreb, Croatia

COOPERATION - INSTITUTIONS


  1. Name of institution: Klinička bolnica "Merkur"
    Type of institution: University/Faculty
    Type of cooperation: Joint publishing of scientific papers
    City: 10000 - Zagreb, Croatia

  2. Name of institution: Klinika za dječje bolesti Šalata
    Type of institution: University/Faculty
    Type of cooperation: Joint project
    City: 10000 - Zagreb, Croatia
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