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Chromosomenaberrationen, Geschwülste und Entwicklungsstörungen

  • A. Gropp
Part of the Verhandlungen der Gesellschaft deutscher Naturforscher und Ärzte book series (NATURFORSCHER, volume 111)

Zusammenfassung

Postnatal neu erworbene, meist auf einzelne Gewebe beschränkte, also „klonale“ Chromosomenanomalien weisen enge Beziehungen zur Entstehung von Tumoren auf: so beim Menschen das sog. Philadelphia Chromosom bei chronischer myeloischer Leukämie und die Anomalie des Chromosoms No 14 bei dem in Afrika vorkommenden Burkitt-Lymphom. Bei der Maus zeigen thymusabhängige Leukämien ein überzähliges Chromosom No 15.

Dem sind konstitutive, bei der Gametenbildung der Eltern entstandene, daher bereits in der Fruchtanlage vorhandene und angeborene Chromosomenaberrationen des ganzen Organismus gegenüberzustellen. In einigen Fällen sind kleinste, spezifische Strukturanomalien dieser Art die Ursache von dysontogenetischen Tumoren, d. h. Tumoren auf angeborener Grundlage. Ein Fall besonderen Interesses stellt die echte Blasenmole dar, die als Tumor der Placenta auf dem Boden der Fehlentwicklung einer Zygote entsteht, die nur väterliche Chromosomen enthält.

Andererseits sind konstitutive numerische und strukturelle Anomalien der Chromosomen beim Menschen in vielen Fällen Ursache für ein frühes Absterben der Fruchtanlage oder für Fehlentwicklungen mit schweren Mißbildungen. Viele Anlagen mit chromosomalen Anomalien sterben in der frühen Fetalperiode ab, andere erst gegen Ende der Schwangerschaft oder bald nach der Geburt. Die in diesem Rahmen auftretenden spontanen Fehlgeburten sind Ausdruck einer selektiven Elimination. Ein längeres Überleben kommt nur dem Down-Syndrom zu, weil die Manifestation der Triplikation des Chromosoms No 21 vergleichsweise mild ist. Trisomien, die beim Menschen die häufigste Chromosomenaberration darstellen, lassen sich in einem Experimentalmodell der Maus spezifisch indizieren. Man kann daran die für den Menschen gültigen Zusammenhänge der Entstehung von Chromosomenaberrationen, der Muster fehlerhafter Entwicklung und der sequentiellen pränatalen Elimination der Anomalien in systematischen Versuchsansätzen analysieren.

Obwohl die Entwicklungsspanne einer Fruchtanlage mit Chromosomenanomalie, z. B. einer Trisomie, meist noch vor oder allenfalls bald nach der Geburt eine Begrenzung findet, muß dies nicht auch für Einzelzellen oder isolierte zelluläre Funktionssysteme zutreffen. Wenn Stammzellen blutbildender Gewebe von trisomen Embryonen auf letal vorbestrahlte Mäuse übertragen werden, können sie die zerstörte Blutbildung des bestrahlten Tieres restaurieren und längeres Überleben gewährleisten. Untersuchungen dieser Art tragen zur Erforschung der Fähigkeiten oder Defekte einzelner Zellsysteme bei konstitutiven chromosomalen Aberrationen bei.

Schlüsselwörter

Dysontogenetische Tumoren Hypoplasie Mißbildung Tiermodell Trisomie Tumorcytogenetik 

Chromosome Abnormalities, Tumours and Developmental Disorders

Summary

Clonal chromosome disorders occurring or acquired at any postnatal age are often closely related with the origin of tumours. In man the Ph1-chromosome (9; 22) anomaly in CML or the 8; 14 translocation in the African malignant Burkitt Non-Hodgkin lymphoma are, among other cases, prominent examples.

On the other hand, constitutive, inherited or novel chromosome anomalies conveyed from the zygote to all tissues of the organism may cause a higher risk for the origin of tumours, Rarely, inheritable minor structural chromosome mutations are known to determine the occurrence of dysontogenetic tumours, as e.g., nephroblastoma, but it is assumed that more such cases will become elucidated in the future. As a special phenomenon, true hydatiform mole is a tumour of the placental tissue due to a disorder of intragenome regulation.

Constitutive or numerical structural chromosome anomalies of man are a frequent cause of early or late abortion or of abnormal development and malformation. Despite the predominating principle of selective fetal elimination, a few anomalies such as Down’s syndrome, may escape to longer survival due to the relatively mild effects of chromosome 21 triplication.

Trisomies which represent in man the most frequent type of chromosome disorders, can be induced, and systematically studied in an experimental model of the mouse. This allows the elaboration of the developmental profiles of all trisomies (and monosomies) of the mouse. Also, the above mentioned principle of selective elimination of abnormal implants can be analysed experimentally.

Although the developmental span of a trisomic zygote is limited, there is evidence that cells and tissues isolated from the chromosomally abnormal organism can survive much longer. Thus, haemopoietic stem cells, at least in Ts 12 and 19 of the mouse, can be rescued from trisomic fetuses by transferring them to lethally irradiated adult mice, whose blood forming organs may eventually become permanently repopulated by the trisomic cell lineage. This type of experiments is suited for closer analyses of potential functions vs. defects of chromosomally abnormal cellular systems, e.g., with regard to growth and development.

Key words

Animal model Dysontogenetic tumours Hypoplasia Malformation Trisomy Tumour cytogenetics 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1981

Authors and Affiliations

  • A. Gropp
    • 1
  1. 1.Institut für PathologieMedizinischen Hochschule LübeckLübeckBundesrepublik Deutschland

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