STATISTICAL-ANALYSIS OF CYTOGENETIC ABNORMALITIES IN HUMAN CANCER-CELLS

It is sometimes difficult to evaluate reports of nonrandom chromosome involvement in certain malignant diseases, since the random or expected distribution is seldom defined. Methods were developed for the statistical analysis of cytogenetic abnormalities in human cancer cells with modal karyotypes in the diploid range (35-57 chromosomes). The expected gain or loss of each chromosome will presumably occur with equal probability, and structural abnormalities will involve each chromosome in proportion to its size. To perform this analysis, the total number of numerical and structural abnormalities is determined from the modal karyotypes of a series of histologically related tumors. The maximum expected values are determined by computer simulation for different levels of significance. Then the distributions of observed and expected abnormalities of each type are compared, to identify nonrandom involvement. Preferential gain or loss is analyzed for each of the 24 different chromosomes, and preferential structural rearrangement is determined for each of the 48 chromosome arms. Two series of karyotypic data were analyzed to demonstrate the utility of this method. The rationale for the assumptions made, as well as alternative approaches, are discussed.