Tumor cytogenetics

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The tumor cytogenetics is a branch of cytogenetics (chromosome research) that deals with the genetic research of tumors is concerned. In particular, chromosome changes in tumor tissue are investigated, which can provide information about the type of tumor and its degree of malignancy . Tumor cytogenetics is of particular importance in the diagnosis of tumor-like diseases of the bone marrow such as B. Leukemia .

history

The beginnings of tumor cytogenetics go back to the 19th century. As early as 1890, the German pathologist David Paul von Hansemann reported on conspicuous structures of the cell nucleus and disturbed figures of cell division in histological sections of carcinoma tissue. He already suspected a connection between these anomalies and the development of cancer. In 1914, the German zoologist Theodor Boveri proposed the chromosome hypothesis of tumor development . After that, chromosome changes in a cell create the conditions for malignant growth. However, it took many years until 1960 for the first time a specific chromosomal abnormality in a human tumor disease could be described. It was named the Philadelphia Chromosome because it was discovered in a Philadelphia laboratory . There it was found that in the cells from the bone marrow of patients with chronic myeloid leukemia (CML) a small, shortened chromosome appears so regularly that its detection can be used for diagnostic purposes. In 1967 it was then possible to prove in meningioma that this benign tumor of the meninges also had a typical cytogenetic change in the form of the loss of an entire chromosome.

The rapid development of cytogenetic banding techniques made it possible in 1972 to prove that a chromosome 22 was lost in meningioma . Chromosome 22 is also affected in the formation of the Philadelphia chromosome, but no chromosome material is lost, instead an exchange of pieces (reciprocal translocation ) takes place between chromosomes 22 and 9 . In the following years, more or less specific chromosomal abnormalities were discovered in a large number of human tumor diseases, which play an important role both in assessing the malignancy and in monitoring therapy. Thanks to new molecular genetic methods, it has become possible to make many of these chromosomal anomalies directly visible in the nuclei of tumor cells without having to carry out a complete chromosome analysis. As a result, specific chromosomal abnormalities in tumor tissue could be detected much more easily and quickly.

With the help of tumor cytogenetics, it has also become possible to localize a whole series of genes in the human chromosome set that are associated with the development of tumors. Is an example of the ABL - oncogene , which is normally on chromosome 9 is located and there acts as strictly regulated growth gene. When the Philadelphia chromosome is formed as part of a 9/22 translocation, this gene is shifted to chromosome 22 in the BCR region, creating a BCR / ABL fusion gene. This gene produces a fusion protein with a tyrosine kinase activity in a largely uncontrolled manner , which stimulates a certain cell type in the bone marrow to increase cell division, resulting in a leukemic cell clone. This finding led to the development of tyrosine kinase inhibitors , which now play an important role in tumor therapy .

literature

  • C. Schaaf, J. Zsocke: Basic knowledge of human genetics . Springer Berlin 2018, ISBN 978-3-662-56146-1
  • J. Murken (Hrsg.): Pocket textbook human genetics . Thieme Stuttgart 2011, ISBN 978-3-13-139298-5
  • JP Huret (Editor): Atlas of Genetics and Cytogenetics in Oncology and Haematology online

Web links

Individual evidence

  1. ↑ by Hansemann D .: About asymmetrical cell division in epithelial cancers and their biological significance . Virchows Archiv A Pathologie, Anatomie Volume 119, 1890, pp. 299-236.
  2. ↑ Boveri T .: On the question of the development of malignant tumors . Gustav Fischer, Jena, 1914.
  3. ↑ Nowell PC, Hungerford DA: A minute chromosome in human chronic granulocytic leikemia . Science Volume 132, 1960, p. 1497.
  4. ↑ Zang KD, Singer H .: Chromosomal constitution in meningiomas . Nature Volume 216, 1967, pp. 84-85.
  5. ↑ Zankl H., Zang KD: Cytological and cytogenetical studies on brain tumors: IV. Identification of the missing G-chromosome in human meningiomas as no. 22 by fluorescence technique. Human Genetics Volume 14, 1972, pp. 167-169.
  6. ^ JD Rowley: Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. In: Nature . Volume 243, Number 5405, June 1973, pp. 290-293, PMID 4126434 .
  7. ^ Zankl H .: Molecular Cytogenetic Tumor Diagnostics . In: (Ed. Raem AM et al): Genmedizin , Springer, Berlin, 2001, pp. 243-264.
  8. ↑ Goldman JM, Melo JV: BCR-ABL in chronic myelogenous leukemia - how does it work? Acta Haematologica Vol. 119, 2008, pp. 212-217.