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Content archived on 2024-04-16

MOLECULAR CYTOGENETICS OF SOLID TUMOURS

Objective

The major goal of the Concerted Action was to use molecular cytogenetics as an approach to develop diagnostic protocols and reagents for a variety of solid tumours. This required the close collaboration of medical doctors, pathologists, cytogeneticists and molecular biologists. A multinational effort is here essential for several reasons, one being the fact that various tumours are relatively rare, so exchange of data and patient material is essential for valuable studies.
Research plymerase chain reaction has been carried out using molecular cytogenetics to develop diagnositic protocols and reagents for a variety of solid tumours. In collaborative studies on neuroblastoma (Nb), a constitutional reciprocal translocation {t (1;17) (p36;q12-21)} found in a patient with neuroblastoma was analysed to find out whether the putative Nb tumour suppressor gene, thought to reside at 1p36, was affected by the translocation. Somatic cell hybrids were established and the presence of the derivative chromosomes was ascertained by karyotyping and fluorescence in situ hybridization (FISH). For the characterization of the chromosomal breakpoints, pulse field gel electrophoresis (PFGE) and FISH were used in collaborative studies and most available DNA markers around the 1p36 were mapped.
A novel approach to the identification of chromosomes has been developed, which is based upon fluorescent in situ identification of human marker chromosomes using flow sorting and Alu element mediated polymerase chain reaction (PCR). Chromosome paints were generated to various normal chromosomes including 5, 6, 14, 19, and 22 and shown to be effective in the identification of the appropriate chromosomes. In addition, certain abnormal chromosomes were used to generate region specific paints.
As an approach to molecularly define chromosome 12g13-15 aberrations observed in lipoma, myxoid liposarcoma, uterine leiomyoma and pleomorphic adenoma of the salivary gland, a molecular and cytogenetic research programme is being carried out by a multinational research consortium. The first step has been the development of cell lines for each of the 4 tumour types and the cells are being used to define molecularly the chromosome break points.
In the proposed research plan the cytogeneticists will first establish, which chromosome regions are consistently involved in genetic aberrations of particular tumour types. The molecular biologists will then define on the molecular level the genetic alterations that have taken place and identify the genes that are affected. On the basis of these data, rapid and highly sensitive diagnostic protocols can be set up using new and advanced molecular cytogenetic technology. Part of this technology, as was expected, had to be developed and/or improved in the context of this Concerted Action. The primary aim of the collaborative programme was the typing of solid tumours by molecular cytogenetics; subsequent correlation studies with histopathological and clinical data might then lead to the identification of prognostic determinants.
%Through the Concerted Action, it was expected that not only greater numbers of rare solid tumours could be studied but also that they could be studied in greater detail. Information that would not be obtained otherwise would become available to the research and medical community.

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CON - Coordination of research actions

Coordinator

University of Leuven
EU contribution
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Total cost

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