Modal Karyotype Research Articles

Chromosome changes in 6-TG-resistant mutant strains derived from a karyotypically stable human line, C32.

Karyotypes of the human C32r16 line and its HPRT-mutant derivatives were compared. All three HPRT-mutant strains (TG-A, TG-E1, and TG-E2) studied were hypotetraploid and arose by genomic duplication. TG-A and TG-E had distinct karyotypes, reflecting their independent clonal origins. Both TG-E1 and TG-E2 were similar karyotypically, except that TG-E2 differed from TG-E1 by the presence of two new sets of balanced translocations and a significantly higher number of new markers, viz., 24 new markers in 14 TG-E2 cells as compared to 2 new markers in 13 TG-E1 cells. Comparison of the hypothetical 2s karyotype of C32r16 with the modal karyotypes of the mutants revealed (1) that chromosome changes occurred more frequently among marker chromosomes (57.1%) than among normal chromosomes (18.1%) and also more frequently among tetrasomic (28.6%) than among disomic (3.3%) normal chromosomes, and (2) that one member of a group of paired marker chromosomes tended to be eliminated very frequently, whereas disomic normal chromosomes retained their disomic condition. Chromosome 7 was involved in the formation of new marker chromosomes twice as much as any other chromosome, and even increased to pentasomy in TG-E1. Chromosome changes associated with 6-thioguanine treatment are briefly discussed.

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. Therefore, we have developed methods for the statistical analysis of cytogenetic abnormalities in human cancer cells with modal karyotypes in the diploid range (35–57 chromosomes). For this analysis, it is assumed that the expected gain or loss of each chromosome will occur with equal probability and structural abnormalities will involve each chromosome in proportion to its size. To perform this analysis, the total number of numberical 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. We have analyzed two series of karyotypic data to demonstrate the utility of this method. The rationale for the assumptions made as well as alternative approaches are discussed.

Emergence of a Cell Line With Extreme Hypodiploidy in Blast Crisis of Chronic Myelocytic Leukemia

Cytogenetic studies in a patient with chronic myelocytic leukemia (CML) demonstrated the emergence of an extremely hypodiploid cell line at the time of blast crisis, a modal chromosome number of 35, with the modal karyotype 35,XY. - 3, -4,-5,-7,-9,-11,-12,-13,-15, - 16,-17,- 19, -20,-22, + t(9:22) (q34;q11). + Mar1 + Mar2, + Mar3. Giemsa-banding confirmed complex chromosome rearrangements and demonstrated distinct banding patterns for the marker chromosomes. Cytologic characteristics of the leukemia blasts were predominantly myeloid. There was no important clinical response to chemotherapy, including vincristine and prednisone, or to radiotherapy.

Emergence of a cell line with extreme hypodiploidy in blast crisis of chronic myelocytic leukemia

Cytogenetic studies in a patient with chronic myelocytic leukemia (CML) demonstrated the emergence of an extremely hypodiploid cell line at the time of blast crisis, a modal chromosome number of 35, with the modal karyotype 35,XY, -3, -4, -5, -7, -9, -11, -12, -13, -15, -16, -17, -19, -20, -22, + t(9;22) (q34;q11, + Mar1, + Mar2, + Mar3. Giemsa-banding confirmed complex chromosome rearrangements and demonstrated distinct banding patterns for the marker chromosomes. Cytologic characteristics of the leukemia blasts were predominantly myeloid. There was no important clinical response to chemotherapy, including vincristine and prednisone, or to radiotherapy.

Genetic studies on human lymphoblastoid cell lines: isozyme and cytogenetic heterogeneity in a cell line, with evidence for localization of the Pep A locus in man

One hundred and thirty-three clones (60 mutagen treated, 73 controls) of the human male lymphoblastoid cell line F 137 have been examined for the electrophoretic pattern of more than 30 enzymes. In nine instances there was loss of activity of one allele of an X-linked or heterozygous autosomal locus. Seven of these involved the Pep A locus, and in every case the change was from the Pep A 2-1 phenotype to Pep A 2. Cytogenetic analysis of the parent line revealed a number of variants on the modal karyotype. On cloning, there appeared to be some selection for survival of non-modal cells. The proportions of the cytogenetically distinct populations within the bulk culture varied over a period of many months. There was a strong correlation in individual clones between loss of activity of the product of the Pep A1 allele and the presence in the cells of a 9/18 translocation. In addition there was one clone of phenotype Pep A 2 with a deletion of part of the long arm of chromosome 18. The data confirms the assignment of the Pep A structural locus to the distal half of the long arm of chromosome 18 and localizes it with some precision to the qter region. The Pep A 2 phenotype of the clones containing the 9/18 translocation could be the result of a small deletion eliminating the Pep A1 allele but not large enough to be detected cytogenetically. Alternatively inactivation of the Pep A1 allele may have occurred as a position effect resulting from the close association of heterochromatin from the centromere of 9 with the qter region of 18.

The effects of growth in vitro on the chromosome complement of Daucus carota (L.) suspension cultures

The chromosome number distributions and modal karyotypes of several suspension culture lines of Daucus carota L. have been analysed at various times after initiation. All lines had stable modal chromosome numbers and karyotypes, with small but significant variation about the modes. Some lines showed a predominance of diploid cells with a karyotype similar to the plant. Polyploid multiples of the modal chromosome number were present in all lines at low frequency. Variation of the 2,4-D concentration in the culture medium produced little alteration of the chromosome number distributions, but omission of 2,4-D produced a significant drop in the frequency of multipolar mitoses in those culture lines in which this treatment induced differentiation. There was no evidence of any direct effect of 2,4-D on general mitotic dynamics. Alteration of the frequency with which cultures were transferred to fresh medium showed that stationary phase was critical in the maintenance of the low frequency of tetraploids present in a predominantly diploid culture line. The results are explicable in terms of a competitive selection for cells with the dominant modal chromosome number in the presence of various mechanisms continuously producing polyploid, aneuploid and structurally altered karyotypes.

Studies of a cell line derived from a human malignant melanoma.

Employing in vitro methodology and new staining techniques, changes in karyotype of a heteroploid tumor cell line derived from a pulmonary metastasis of a malignant melanoma were studied over 10 months of continuous cultivation. The modal karyotype of tumor cells in a 3-week-old culture was composed of 41 intact and 11 marker chromosomes. These markers contained three paired (disomic) and five other (monosomic) elements. The derivative cell populations in 5- to 10-month-old cultures showed changes merely in the paired markers from disomy to monosomy, by loss of one element or by formation of a new marker chromosome. Prolonged treatment in a defined medium completely devoid of serum resulted in a selection of heteroploid cells and suppression of diploid fibroblasts. The heteroploid cultures were further enriched by collecting freely suspended cells. Growth of tumor and normal cells in mixed culture had no apparent influence on either cell type.

Karyotypic analysis of a near-diploid established mouse cell line.

A near-diploid mouse ceil line has been produced from C57BL/6J X AKR/J F<sub>1</sub>-hybrid embryonic cells by spontaneous transformation. The modal chromosome number of this line is 41 (2n = 40), with low numerical and structural variation relative to other mouse lines which have been reported. Giemsa-banded karyotypes on a number of clones and subclones from this line have been analyzed. The modal karyotypes deviate very little from that of a normal diploid female. Most of the cells have two X chromosomes, one of which is unlabeled early in the S phase.

Chromosome Patterns in Mouse Lung Tumors

The chromosomal constitutions of spontaneous pulmonary adenomas of strain A mice and of pulmonary adenomas from strain A animals treated with urethan were analyzed in detail. Stemlines of the primary pulmonary adenomas were diploid, pseudodiploid, and aneuploid, with a preponderance of aneuploid. Tumors having a diploid mode also had cells with abnormal karyotypes. These observations emphasize that either a superficially normal or abnormal modal karyotype may be present at the preneoplastic stage. Serially transplanted adenomas underwent further alteration of stemlines which may or may not reflect tumor progression. Whether or not the abnormal chromosome constitutions have primary oncogenic significance, they may facilitate clonal selection during tumor progression.