Relationship between tumorigenicity and the dosage of lymphoma- vs. normal-parent-derived chromosome 15 in somatic cell hybrids between lymphoma cells with rearranged pvt-1 gene and normal cells

Somatic cell hybrids were generated between YACUT, a doubly drug-resistant subline of YAC-1 (a Moloney-virus-induced T-cell lymphoma of strain A/Sn origin with 2 proviral insertions near the pvt-1 locus) and normal diploid fibroblasts of CBAT6T6 origin. Three independent fusions were performed. Three uncloned hybrid cultures and 9 independently-derived clones were tested for tumorigenicity by the inoculation of graded cell numbers into syngeneic hosts. One of 3 uncloned hybrid cultures and 3 of 9 clones were weakly tumorigenic (take incidence 0%), and 1 of 3 uncloned hybrid cultures and 6 clones were highly tumorigenic (take incidence greater than 80%). One weakly tumorigenic hybrid and 3 weakly tumorigenic clones carried 3 copies of the tumor-derived chromosome 15 and 2 copies of the normal fibroblast-derived t(14;15) chromosomes. In contrast, 2 highly malignant hybrid clones lost one copy of the normal-fibroblast-derived t(14;15), but contained increased numbers (3.44-4.44) of the tumor-derived chromosome 15. Four tumorigenic segregants selected from the weakly tumorigenic fibroblast hybrids by in vivo inoculation showed the same cytogenetic change as the highly tumorigenic hybrid clones, in that the ratio of the normal:tumor-derived chromosomes 15 changed from 1.18-1.55 to 4.11-5.71. Tumorigenicity was thus associated with a modified balance between the tumor vs. the normal-parent-derived 15-chromosomes. Instead of the usual 3:2 ratio, the tumor-derived 15-chromosomes increased disproportionately, whereas the relative number of the normal-parent-derived 15-chromosome decreased, as a rule. These results suggest that amplification of the lymphoma-derived chromosome 15 favors tumorigenicity, but that this effect is counteracted by some influence emanating from the normal-parent-derived homologous chromosome.     

Suppression of transformed phenotypes in intraspecific somatic cell hybrid clones between the c-myc activating mouse plasmacytoma line and normal cells

The role of normal-cell-derived chromosome 15 in suppressing transformed phenotypes was studied in intraspecific hybrid clones between the c-myc oncogene activating BALB/c mouse plasmacytoma (S194) cells and normal spleen cells or fibroblasts from CBA/H-T6 mice. All the hybrid clones between S194 and normal spleen cells grew very rapidly in suspension and formed colonies in soft agar. In contrast, the hybrid clones between S194 and normal fibroblasts grew slowly in an attached form. They were divided into 2 groups on the basis of their morphology and growth properties: most clones showed flat type morphology, and no colony formation was seen in soft agar, while some clones grew in a piled-up fashion and formed colonies in soft agar. The hybrid clones between S194 and normal spleen cells lost some normal-cell-derived chromosomes but retained most tumor-derived marker chromosomes including the t(12;15) chromosome which carried the activated c-myc oncogene. On the other hand, hybrid clones between S194 cells and normal fibroblasts retained almost all chromosomes from both parental cells. With respect to retention of normal-cell-derived chromosome 15, both the flat and piled-up type clones retained 2 copies each of the t(14;15) and T6 marker chromosomes, the normal counterparts of the t(12;15) chromosomes. Our results suggest that the transformed phenotypes of the hybrid clones between S194 cells and normal fibroblasts are negatively modulated by normal-cell-derived chromosomes but not by normal-cell-derived chromosome 15 alone.     

Somatic cell hybrids of the Djungarian hamster: malignancy and evolution of the karyotype

Djungarian hamster somatic cell hybrids were obtained by fusing malignant SV40-transformed fibroblasts (line DM15, HGPRT-), and normal male lymphoid cells. Tumorigenicity, growth in soft agar and karyotype changes of 10 independent hybrid clones were studied. All hybrids grew as tumors after injection of new-born hamsters with 1 x 10(6) cells. A total of 313 tumors occurred in 523 hamsters. The hybrids proliferated in soft agar as well. No correlation was noted between the ability of hybrids to grow in vivo and to form colonies in soft agar. The total chromosome number in hybrid cells was usually less than the expected sum of the parental chromosome sets. G-banding analysis showed that, in vitro, hybrids lost chromosomes of the normal parent, whereas marker chromosomes of the malignant parent were retained. In the majority of hybrid tumors the chromosome set was reduced to the diploid range. In tumors with a slightly reduced karyotype one or two homologues of chromosomes #4 and #8 were, as a rule, eliminated.     

Chromosomes 6 and 18 induce neoplastic suppression in epithelial ovarian cancer cells

Metaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13, 14, 15 and 18 are frequently deleted in primary ovarian cancers (OCs). Therefore we used microcell‐mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes into 2 epithelial OC cell lines (TOV112D and TOV21G). The in vitro neoplastic phenotype (measured as anchorage dependent and independent growth and invasion) was compared between recipient OC cell lines and multiple MMCT hybrids. Chromosomes 6 and 18 showed strong evidence of functional, neoplastic suppression for multiple hybrids in both cell lines. We also found evidence in 1 cancer cell line suggesting that chromosomes 4, 13 and 14 may also cause functional suppression. Array CGH and microsatellite analyses were used to characterise the extent of genomic transfer in chromosome 6 and 18 hybrids. A 36 MB deletion on chromosome 6 in 2 hybrids from 1 cell line mapped the candidate region proximal to 6q15 and distal to 6q22.2; and an ～10 MB candidate region spanning the centromere on chromosome 18 was identified in 2 hybrids from the other cell line. These data support reported functional effects of chromosome 6 in OC cell lines; but to our knowledge, this is the first time that functional suppression for chromosome 18 has been reported. This suggests that these chromosomes may harbour tumour suppressor‐“like” genes. The future identification of these genes may have a significant impact on the understanding and treatment of the disease and the identification of novel therapeutic targets. © 2008 Wiley‐Liss, Inc.     

The role of chromosome 15 in murine leukemogenesis. II. Relationship between tumorigenicity and the dosage of lymphoma vs. normal-parent-derived chromosomes 15 in somatic cell hybrids

Somatic cell hybrids were generated between an MCF-virus-induced 15-trisomic T-cell lymphoma of AKR origin with a proviral insertion near the c-myc locus, and normal diploid fibroblasts or lymphocytes of CBAT6T6 origin. Three lymphoma/fibroblast fusions were performed. Six independently-derived clones from 2 fusions were tested for tumorigenicity. Three of the 6 clones were weakly malignant (take incidence 20% below), and 3 were strongly malignant (take incidence over 80%). All 3 lymphoma/lymphocyte hybrids and 6 derived clones were strongly malignant. All hybrids contained a nearly complete chromosomal complement of both parental cells. This was confirmed at the molecular level by determining the ratio of germ-line (G) vs. rearranged (R) myc-carrying Eco RI fragments that showed the expected 1.9-2.7:1 proportion. Malignant segregants selected from the weakly malignant lymphoma/fibroblast hybrids by in vivo inoculation showed changed 15-chromosome ratios. Four out of the 6 clones showed amplification of the lymphoma-derived 15-chromosome that carries the R-myc fragment and a concomitant decrease in the average number of the G-myc-carrying chromosomes. This was deduced from the fact that the G:R ratio was between 2 and 3:1 in the in vitro hybrids but became inverted (1:2-3) in the tumors. Two tumors showed no amplification of R-myc. G-myc was decreased. One of these tumors showed a change in the G:R ratio from 2.5:1.0 to 1.2:1.0, while the other was essentially unchanged (1.9:1.0 in the in vitro clone and 2.2:1.0 in the derived tumor). These findings support the notion that both the amplification of the lymphoma-derived 15-chromosome with the retrovirally rearranged c-myc carrying fragment and/or the loss of the G-myc-carrying 15-chr can contribute to the tumorigenic potential of the hybrids.     

Non-random duplication of chromosome 15 in murine T-cell leukemias: Further studies on translocation heterozygotes

Four combinations of translocation heterozygotes with cytogenetically distinct chromosomes 15 were used to investigate whether the T-cell leukemia-associated duplication of chromosome 15 is a non-random or a random event. In leukemias of AKR X CBAT6T6 F₁ (Group I) and C57BL X CBAT6T6 F₁ (Group IV) crosses the duplication was non-random, affecting the AKR-derived chromosome 15 (Group I) and CBAT6T6-derived T (14;15) 6 chromosome (Group IV), respectively. In contrast, in leukemias induced in CBA X CBA T6T6 F₁ combinations (Group III) - where both chromosomes 15 (normal and translocated) were CBA-derived - the duplication was random. Similarly, in the Rb6;15 X CBAT6T6 F₁ cross (group II) the duplication of chromosome 15 appeared to be random. The results supported the hypothesis that the genetic content of chromosome 15 rather than its translocated state is decisive for the preferential duplication of this chromosome in T-cell leukemogenesis. However, the genetic background of the strain from which chromosome 15 is derived may also influence the duplication pattern of individual tumors.     

Inheritance of immunogenicity and metastatic potential in murine cell hybrids from the T-lymphoma ESb08 and normal spleen lymphocytes

T-lymphoma cells were fused with normal lymphoid cells to examine the segregation of tumorigenicity and metastatic capacity in the hybrids. In independent fusions the immunogenic ESb08 T-lymphoma line fused successfully with normal syngeneic spleen cells (from DBA/2 and CD1 mice) enriched either with T-cells or B-cells. Ten times fewer hybrids were obtained with B-cells compared to the number obtained with T-cells, and marker assays showed that both types of fusions preferentially generated T-T hybridomas. Some of the hybrids resembled their tumor parent in their ability to form primary and secondary tumors only in irradiated DBA/2 mice, whereas other hybrids lost the high ESb08 immunogenicity, were equally tumorigenic, and in some cases metastatic, in nonirradiated mice. DNA distributions of the original hybrid lines ranged from a hexaploid DNA content (expected for complete hybrids derived from a tetraploid line and normal diploid cells) to a tetraploid DNA content, confirming the reported chromosome instability of T-T hybrids. No correlation was noted between the initial DNA content and tumorigenicity, but in the case of complete hybrids, reduction in the ploidy levels always was observed in the cells of primary and metastatic lesions. One chromosomally stable and highly malignant hybrid (C2), which was analyzed for segregation of chromosomes and for drug-resistance markers, showed preferential loss of chromosomes from the normal T-cell fusion partner. The decreased immunogenicity of this hybrid could not be related to any detectable loss of chromosomes from the ESb08 tumor parent.     

Karyotypic changes with neoplastic conversion in morphologically transformed golden hamster embryo cells induced by X-rays

Chromosomes from nine morphologically transformed (MT) cell lines (designated MT14 to MT22) of Golden hamster embryo cells induced by X-rays and from tumor-derived cell lines (MT14T to MT22T), obtained after injection of MT cells, were analyzed by the Giemsa banding method. MT cell lines showed a variety of numerical abnormalities. All of the MT cell lines involved trisomy of chromosomes 11 (80 to 100% of cells in each cell line) and 3 (8% of MT22 cells and 100% in other cell lines). Although the latent period for tumor growth differed greatly, eight of nine MT cell lines (MT14 to MT21) produced tumors at the site of injection. All tumor-derived cell lines involved trisomy of chromosome 3 at a 100% rate of incidence. Seven of nine tumor-derived cell lines (MT15T to MT18T, MT20T to MT22T) lost one chromosome 11 from the trisomic condition, resulting in disomy of chromosome 11. These results suggest that trisomies of chromosomes 11 and 3 may play a role in X-ray-induced neoplastic progression.     

Multiple chromosomes carrying tumor suppressor activity for a uterine endometrial carcinoma cell line identified by microcell-mediated chromosome transfer

Putative tumor suppressor genes can be mapped to specific chromosomes by the introduction of individual chromosomes derived from normal cells via microcell fusion. We have examined whether a highly malignant human uterine endometrial carcinoma cell line, HHUA, can be suppressed by only one normal chromosome or by multiple chromosomes. A library of mouse A9 clones containing different human chromosomes tagged with the pSV2-neo plasmid DNA were constructed. Transfer by microcell fusion of either chromosome 1, 6, 9, 11, or 19 into the HHUA tumor cell line was performed, and the abilities of the microcell hybrids to form tumors in nude mice were examined. The introduction of a chromosome 19 had no effect on the tumorigenicity of the cells, whereas microcell-hybrid clones with an introduced chromosome 1, 6 or 9 were completely suppressed for tumorigenicity. A decrease in tumor-take incidence in some but not all clones was observed following the introduction of a chromosome 11. The nontumorigenic microcell hybrids with an introduced chromosome 1 differed from the nontumorigenic microcell hybrids with an introduced chromosome 6, 9, or 11. A large percentage of hybrids with chromosome 1 senesced and/or showed alterations in cellular morphology and transformed growth properties in vitro. No growth or morphology alterations were observed following transfer of the other chromosomes. These results may indicate that more than one chromosome carries a tumor suppressor gene(s) for this human uterine endometrial carcinoma cell line and support the hypothesis that multiple tumor suppressor genes control the tumorigenic phenotype in the multistep process of neoplastic development.     

Non-random duplication of chromosome 15 in murine T-cell leukemias induced in mice heterozygous for translocation T(14:15)6.

Trisomy of chromosome 15 is a highly regular feature of murine T-cell leukemogenesis. We have studied the chromosomal constitution of 7,12-dimethylbenza(a)anthracene (DMBA)-induced T-cell leukemias in C57BL X CBAT6T6 F1 mice. The CBAT6T6-derived chromosome T(14:15)6 was regularly duplicated whereas the C57BL-derived normal chromosome 15 was only present in one copy. It was concluded that the gene(s) that tend to duplicate in parallel with the neoplastic transformation of the prothymocyte to an overt leukemic cell have a greater chance of duplicating and/or may have a stronger promoting effect on leukemogenesis if stronger promoting effect on leukemogenesis if located on the CBA-derived, structurally rearranged T(14:15)6 than the corresponding genes located on the C57BL-derived normal chromosome 15.     

Chromosome 15 trisomy in spontaneous and carcinogen-induced murine lymphomas of B-cell origin

G-banding analyses of 14 independently derived B-cell lymphomas showed the frequent occurrence of chromosome 15 trisomy. It was present in seven of nine spontaneous B-cell lymphomas, but in company with other trisomies, monosomies and marker chromosomes. In five carcinogen-induced primary B-cell leukemias, trisomy 15 was the dominating change. Taken together with the previously demonstrated importance of chromosome 15 trisomy for T-cell leukemogenesis and of the 12;15 translocation in plasmacytogenesis in the mouse, it appears likely that the distal part of chromosome 15 carries a cluster of genes, perhaps a supergene region, that may play an important role in the differentiation and/or the normal responsiveness of various lymphoreticular cell types to growth control.     

Modification of myc gene amplification in human somatic cell hybrids

In order to study whether cell fusion would modify the DNA copy number of an amplified oncogene, somatic cell hybrids were made between the human neuroepithelioma cell line MCIXC and HeLaCOT human adenocarcinoma cells. MCIXC contains approximately 21 copies of the c-myc oncogene and HeLaCOT contains approximately 5 copies relative to the control. All hybrid clones investigated displayed a marked decrease in the number of copies of c-myc DNA (an average of 5 copies), while the level of c-myc RNA in the hybrids was similar to that found in both parents. All eight hybrid clones were found to be completely nontumorigenic even though both parent cells formed tumors in 100% of the nude mice treated by injection. This loss of oncogene amplification in the hybrids was shown not to be due to either heterogeneity of c-myc amplification in the MCIXC parent or segregation of a copy of the chromosome 22 from the hybrids. This loss most likely resulted from the breakdown of a homogeneously staining region (containing the amplified gene copies) into double minutes, which were subsequently lost from the cells. The HeLaCOT cell line was also fused to the human neuroblastoma BE(2)C, which contains approximately 123 copies of the N-myc oncogene relative to control. Ten hybrid clones were found to contain an average of 47 copies of N-myc DNA, significantly less than the 91 copies predicted had no loss occurred. These BE(2)C x HeLaCOT hybrids expressed on average about 15% the N-myc RNA seen in the BE(2)C parent and, as with the MCIXC x HeLaCOT hybrids, were found to be completely nontumorigenic. However, upon passage in culture, one BE(2)C x HeLaCOT hybrid eventually became tumorigenic. This hybrid also displayed reduced copies of N-myc DNA in comparison to its parent hybrid but surprisingly showed a 2-fold increase in N-myc RNA. Thus, the expression of N-myc, but not the amplification state of either myc gene, appears to correlate with the tumorigenicity of the cells.     

Suppression of tumorigenicity in somatic cell hybrids. II. Human chromosomes implicated as suppressors of tumorigenicity in hybrids with Chinese hamster ovary cells

Nontumorigenic diploid human cells were fused with tumorigenic Chinese hamster ovary cells (CHO), and the hybrids were tested for tumorigenicity to determine if specific human chromosomes are associated with suppression of tumorigenicity in cell hybrids. Chromosome complements of cells of 62 nontumorigenic and 45 tumorigenic hybrids (divided into those of low, medium, and high tumorigenicity) as well as 44 tumors derived from the tumorigenic hybrids were determined by both analysis of banded chromosomes and assays of gene markers. Although no single human chromosome was consistently associated with the suppressed phenotype, chromosome 2 was never found in tumor cells, and chromosomes 9, 10, 11, and 17 were found at very low incidences in tumor cells, which suggested that they carry tumorigenicity suppressor information. Since not all suppressed hybrids contained these chromosomes, it is likely that they suppressed tumorigenicity only in combination with each other or other chromosomes. Nine chromosomes in 12 pairwise combinations of nonhomologous chromosomes were not found in tumor cells and were found at an incidence of 5% or less in hybrids of both medium and high tumorigenicity. Other experiments implicated 11 of these combinations involving only 8 chromosomes (chromosomes 4, 7, 8, 9, 10, 11, 13, and 17) as those primarily involved in suppression. Whether chromosome 2 requires another chromosome to effect suppression could not be determined. Further evaluations of the implicated suppressors, including selection of tumorigenic segregants from a panel of suppressed hybrids, again implicated the same chromosomes and their combinations in suppression. Oncogenes have been mapped to many of these chromosomes, and they are frequently involved in tumor-type-specific numerical or structural abnormalities in human neoplasias. The combined evidence suggests that specific human chromosomes of a normal cell carry genes that can regulate several cell phenotypes necessary for the expression of tumorigenicity.     

Gain of chromosomes 15 and 19 is frequent in both mouse hepatocellular carcinoma cell lines and primary tumors, but loss of chromosomes 4 and 12 is detected only in the cell lines.

Chromosomal alterations were investigated in hepatocellular carcinoma cell lines, primary tumors and liver epithelial cell lines derived from normal livers of C57BL/6JxC3H/HeJ F(1) and C3H/HeJxC57BL/6J F(1) mice. In the primary tumors, non-random gain of chromosomes 15 and 19 was found in seven and five of 14 hepatocellular carcinomas, respectively. On the other hand, in the cases of both liver epithelial and hepatocellular carcinoma cell lines, frequent changes were loss of chromosomes 4 (4/9 cell lines) and 12 (3/9) as well as gain of chromosomes 15 (5/9) and 19 (4/9). These results indicate that the chromosomal gain is associated with both in vivo carcinogenesis and establishment of cell lines, while the loss is specific for the latter. PCR analysis using polymorphic microsatellite DNA markers revealed that the loss of chromosome 12 as well as chromosome 4 was much more frequent for the C57BL/6J hepatocarcinogenesis-resistant rather than the susceptible C3H/HeJ strain.     

Specificity of the deletion of chromosome No. 15 in mouse plasmacytoma: brief communication

Q-banding studies in two independent hyperdiploid mouse plasmacytomas, 63-1 and the NP-38-ABCD subline of MSPC-1, revealed that deletion of a No. 15 chromosome was common. The deletion of No. 15 appeared to result from a translocation between No. 12 and 15 in the NP-38-ABCD, as in most plasmacytomas. In 63-1, however, No. 10 was probably a recipient chromosome of the missing segment from the deleted No. 15, and both chromosomes No. 12 remained intact. These karyotypic features suggest that the deleted No. 15 is a tumor-specific marker chromosome in mouse plasmacytoma and that an abnormality of No. 12 is not essential for development of the tumor. The constitution of chromosomes in the two plasmacytomas remained remarkably stable in their homogeneous modal population.     

Spontaneous expression of murine endogenous viruses in hamster X mouse hybrid cells.

The spontaneous expression patterns of murine leukemia virus (MuLV) from mouse spleen cultures and hamster × mouse spleen hybrid cells were compared. The hybrid cells preferentially segregated mouse while retaining a complete set of hamster chromosomes. Virus expression patterns showed considerable mouse strain differences in both parental and hybrid cells. None of 13 BALB/c spleen cultures expressed virus while 6 of 20 hybrid clones expressed N-tropic or N-tropic and X-tropic viruses. All AKR spleen cultures and 5 of 7 hybrids expressed N-tropic but not X-tropic virus. X-tropic virus expression was detected in all 6 NZB spleen cultures and in 5 of 8 hybrids. Virus expression did not occur in NIH Swiss or NIH Swiss/Nude (nu/nu) spleen or hybrid cultures. A major structural locus (Akv-1) for N-tropic virus expression has been assigned to chromosome 7 in AKR mice by recombi-national genetics and is closely linked to the gene for glucose phosphate isomerase (Gpi-1). Analysis of AKR hybrids confirmed the requirement of chromosome 7 for initial expression of mouse N-tropic virus and, in addition, excluded the role of all other mouse chromosomes in this phenomenon. Eighteen of 20 BALB/c clones retained chromosome 7, including 6 virus-positive clones, suggesting that chromosome 7 may be necessary but is not sufficient for N-tropic virus expression in this strain. Hybrid clones with examples of asynteny were found for all other chromosomes. Long-term passage and sub-cloning studies of AKR and BALB/c virus-positive hybrids indicated that virus-positive clones segregated independently of chromosome 7 markers. Spontaneous expression of X-tropic virus in NZB hybrid clones was syntenic with the gene for-enylate kinase (Ak-1) which is assigned to chromosome 2. A relatively small number of NZB hybrid clones were studied and, a firm gene assignment cannot be made, because only one discordant clone each was found for chromosomes 1, 3, 10, 19. Our studies indicate that spontaneous expression of MuLV strains does not require the following MuLV-related genes: Fv-1 (chromosome 4), Fv-2 (chromosome 9), Rec-1 (replication of ecotropic virus, chromosome 5), Gv-1 and H-2 (chromosome 17).     

Further studies on the asymmetry of chromosome 15 duplication in trisomic leukemias of heterozygous origin: preferential status of the AKR chromosome

Four combinations of translocation heterozygotes with cytogenetically distinct chromosomes 15 were used to investigate whether the T-cell leukemia-associated preferential duplication of the AKR-derived chromosome 15 (AKR-15) is determined by factors within this chromosome, or is due to genes within the AKR genotype, but outside chromosome 15. Two of the four combinations were also used to determine whether the AKR-15 duplication preference could be cancelled by MCF-viremia in permissive F1 hybrids. Chemically and virally induced 15-trisomic leukemias showed the same AKR-15 duplication preference, which was due to some autonomous property of AKR-15 itself. It was maintained in (C57BL 6;15 X C57BL) F1 leukemias, where 6;15 is the only AKR-derived chromosome propagated on the C57BL/background. In the (C57BL 6;15 X AKR) F1 hybrid cross where both chromosomes 15 are of AKR origin, duplication occurred at random. To approach the second question, MCF viremia was induced by neonatal virus inoculation into permissive (AKR 6;15 X B6Fv-In) F1 hosts. The preferential duplication status of the AKR-derived 6;15 remained unchanged.     

Adult T-cell leukemia. Chromosome analysis of 15 cases

Chromosome studies was conducted on 15 patients with adult T-cell leukemia. Cells with chromosomal abnormality were seen in 14 of the 15 patients. The modal chromosome number was near diploid range in all the patients. The most common abnormality was 14q+ marker chromosome and partial deletion of the long arm of chromosome 6, i.e., 6q-, which were seen in eight and seven cases, respectively. Donor chromosomes involved in the 14q+ marker chromosome varies, i.e., Yq, #5p, #5q, #9q, #10q or #12q, except for two patients whose donor chromosome origins were unable to determine. The break point in 14q+ marker chromosome was band at q32. The 6q- chromosome was due to a deletion in one patient and interstitial deletion in six patients. A 14q- chromosome having break point at q24 was found in one patient and duplication of Yq chromosome in two patients. In addition, four patients showed a 5q- chromosome or a 9q- chromosome which was due to a translocation or deletion. The significance of these chromosome abnormalities was discussed.     

Karyotype analysis of a human mammary sarcoma explant in vitro

Summary Karyotype of a fibroblastic SH-1 cell line derived from a human mammary sarcoma had 86 (80–92) chromosomes including 6 (4–7) markers, and a various number of double minutes. There were generally even numbers (e.g., 2, 4, etc.) of chromosomes in 17 intact and 3 common marker chromosomes. The t(3;14) and del(14), which had 2 each pers cell genome, were probably formed by the balanced translocation between nos. 3 and 14. Three other markers were single and contained a partial or entire no. 1. The presence of these latter markers was often accompanied by the decrease in the number of the intact no. 1, indicating that no. 1 was the only chromosome actively engaged in rearrangements during this stage of karyotypic diversification. Of the no. 2 and 7q that were over-represented on the per cell level, the 7q had a similar observation from many other solid tumors found in this and other laboratories. In contrast, none of the under-represented chromosomes had the concordant changes consistent to other tumors, although the frequent involvement of no. 9 in the chromosome rearrangements was seen in some human heteroploidies. Address for reprints: Dr. T.R. Chen, American Type Culture Collection, 12301 Parklawn Dr., Rockville, MD 20852.