Clonal chromosome abnormalities in neoplastic cells: evidence of genetic instability?
All types of neoplasia that have been extensively examined, be they benign or malignant, are characterized by acquired chromosomal aberrations. In many instances, the changes are specific for the tumour type in question. Some tumours, even among the most malignant ones, have only a single chromosomal abnormality, whereas others have numerous secondary aberrations. Although an overall parallel exists between a tumour's malignancy and the number and complexity of its chromosomal changes, in some situations altered selection pressure may give rise to reduced karyotypic complexity with time. The effective causes of both primary and secondary chromosomal changes of neoplastic cells are largely unknown. In some special situations, in particular therapy induced acute leukaemias, exposure to a carcinogenic agent seems to have specifically induced the leukaemogenic genetic rearrangement. Patients carrying malignant neoplasms have in most studies been found to have normal chromosomal stability in their non-neoplastic somatic cells, both generally and at the genomic regions that are rearranged in their tumours. Although abnormal chromosomal fragility of cells belonging to the neoplastic parenchyma has not been convincingly demonstrated, the existence of such instability remains a viable, perhaps even necessary, hypothesis. To look for a unifying mechanism common to all neoplastic processes seems simplistic: specific mutagenesis giving rise to both primary and secondary chromosomal changes is likely to occur in some tumours, whereas in others random aberrations are generated, and at least as far as the secondary ones are concerned often at a higher than normal rate, followed by Darwinian selection for fitness within the host organism.
Heim
S
S
Department of Genetics, Norwegian Radium Hospital, Oslo.
D000208:Acute Disease; D001943:Breast Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D015179:Colorectal Neoplasms / Q000235:genetics*; D003240:Connective Tissue Diseases / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics