Chromosome abnormalities as primary events in human malignant disease: evidence from marker chromosomes.

Observations on the chromosomes of cells from 5 human malignant tumors are reported. Each tumor had one or more distinctive marker chromosomes. Marker chromosomes were present in a total of 700 of 711 metaphases from these tumors, which included an early malignant lesion of the cervix showing minimal invasion. Two tumors (a Stage 4 carcinoma of the cervix and a reticulum cell sarcoma, both untreated) yielded preparations of high quality. The 7 best-spread metaphases from the former with the modal number of chromosomes (60) had identical karyotypes, as did 16 from the latter with the modal number of 49. Less extensive data on 13 other tumors, 8 of which had marker chromosomes, are also presented. The data presented here, together with the published data on the chromosomes of cells from human tumors, support the view that human malignant tumors frequently but not invariably arise from a single cell in which chromosome changes have occurred. A carcinoma of the corpus uteri, to which brief reference is made, is a possible exception: Most metaphases had apparently normal karyotypes. The role of chromosome abnormalities (particularly structural changes) in the malignant transformation is discussed. Possible parallels between the chromosome findings in the cells of malignant tumors and those in chronic myeloid leukemia are considered. It is suggested that in tumors there may be both specific changes (perhaps involving chromosomes structurally changed) and coincidental changes. Variation in the coincidental changes might largely account for the wide differences between the karyotypes of different tumors.