PubMed · 1966 · 281 citations · 0 references
Life SciencesGeneticsOncologyCancer GeneticsCytogeneticsNeoplasiaCancer CytogeneticsChromosomal AberrationsChromosomal AbnormalitiesChromosomal DisordersChromosome AberrationsMalignant NeoplasmsCancer Causation EvidenceCytogenetic AberrationsKaryotypic AbnormalitiesLeukemia CytogeneticsNeoplastic CytogeneticsNeoplastic DiseaseNumerical Chromosomal AbnormalitiesNumerical Karyotype Abnormalities
Human neoplasia displays highly variable karyotypes, with no consistent chromosomal pattern across cancers or leukemias except chronic myelocytic leukemia, suggesting that chromosomal changes are likely secondary to the disease process. The study proposes that detailed analysis of isolated chromosomes and their ultrastructure and metabolism could clarify the role of genomic changes in cancer causation. The authors conclude that, except for the Ph1 translocation in chronic myelocytic leukemia, gross chromosomal abnormalities are unlikely to directly cause neoplasia.
Summary Human neoplasia is a heterogenous group of diseases, and hence it is not unexpected that the karyotypic findings in cancer and leukemia are protean in nature. The chromosomal constitutions in these conditions ranges from diploidy, impressive hypodiploidy, to high hyperploidy. Except for chronic myelocytic leukemia, no consistent karyotypic picture has emerged for any group of cancer or leukemia. As a matter of fact, no 2 similar karyotypes have been found in human cancer (primary and metastatic). These findings coupled with the high frequency of diploidy in acute leukemia indicate that gross genomic aberrations cannot be imputed as being involved in the direct causation of neoplasia. The Ph1 chromosome in chronic myelocytic leukemia appears to be the only plausible case for the direct participation of a chromosomal abnormality in the causation of a cancerous state. Even though the possibility exists that submicroscopic gene involvement may induce gross chromosomal changes, the latter leading to the initiation of cancer or leukemia, it is more likely (at least in the author9s mind) that the chromosomal abnormalities in these diseases described to date are secondary phenomena to the neoplastic state. Thus, the escape of the cancerous cell from normal growth controls is due to genic malfunction and the karyotypic changes are mere epiphenomena of the metabolic parameters resulting from the abnormal growth. Future studies on isolated human normal and abnormal chromosomes, ultrastructural and metabolic, may shed considerable light on the role of genomic changes in cancer causation.