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PubMed1999

A novel, non-nested reverse-transcriptase polymerase chain reaction (RT-PCR) test for the detection of the t(15;17) translocation: a comparative study of RT-PCR cytogenetics, and fluorescence In situ hybridization.

BACKGROUND: The development of a rapid and simple reverse-transcription polymerase chain reaction (RT-PCR) assay is described that identifies the promyelocytic leukemia- retinoic acid receptor alpha (PML-RARa) hybrid messenger RNA (mRNA), a characteristic feature of acute promyelocytic leukemia (APL). METHODS AND RESULTS: Randomly primed complementary (cDNA) is synthesized from leukocyte RNA and amplified in the presence of Taq Gold in 2 separate reaction tubes containing primer pairs specific for intron 3 (bcr 3, long [L] form mRNA transcript) and intron 6 (bcr 1, short [S] form)/exon 6 (bcr 2, variant [V] form) breakpoints in PML, respectively. The different sized products generated from each RNA transcript (S, L, or V forms) are readily and unambiguously distinguishable after agarose gel electrophoresis without the need for either nested PCR or hybridization. The sensitivity of the assay is 1 in 10,000 to 1 in 100,000. The separate amplification of a b2-microglobulin transcript controls for adequate RNA and cDNA preparation. The newly developed assay was used clinically for the evaluation of 78 patients with APL. It was rapid and more sensitive than cytogenetic karyotyping, both for the diagnosis of APL and the assessment of minimal residual disease (MRD) after therapy. RT-PCR detected PML-RARa mRNA in all cases positive for the t(15;17) translocation by cytogenetics. However, as many as 50% and 80% of the diagnostic specimens and the specimens for MRD assessment, respectively, that were positive by RT-PCR were negative by cytogenetics. The ratio of cases with L-form to S-form PML-RARa fusion transcript was 2:1, whereas 3 cases (10%) had fusion sites in exon 6 of the PML gene (V forms). In addition, approximately 50% of the patients were diagnosed morphologically with microgranular M3V-type leukemia, but no significant correlation with PML breakpoints was found. CONCLUSION: The current assay is rapid, sensitive, and specific without using nested PCR or hybridization.

Biomarkers, Tumor↗

PubMed1997

Cytogenetic effects in lymphocytes from children exposed to radiation fall-out after the Chernobyl accident.

In a previous paper we reported that a group of children exposed to ionizing radiation following the Chernobyl accident exhibited an appreciable number of chromosome breaks and rearrangements reflecting the persistence of a radiation-induced damage. The results suggested that the children were still exposed to radioactive contamination through consumer foodstuff and life styles. In the present paper, 31 exposed children have been considered together with a control group of 11 children with the aim to confirm previous results. All children underwent whole-body counter (WBC) measures and conventional cytogenetic analysis. The frequency of chromosome aberrations detected by conventional cytogenetics in the group of children chronically exposed to low doses of ionizing radiation resulted in significant differences with respect to the control group. The present work suggests that, for these groups of children, even if the frequency of aberrations is very low and the observation of statistically significant differences is consequently a problem, a persistently abnormal cytogenetic picture is still present several years after the accident.

Child↗

PubMed1998

Cytogenetic monitoring in coke oven workers.

Cytogenetic markers (chromosomal aberrations, sister chromatid exchanges (SCE), cells with high frequency of SCE (HFC), the heterogeneity index SCE (SCE-H) and genetic polymorphism of genotypes GSTM1 and NAT2 were evaluated in the peripheral lymphocytes of 64 coke oven workers and 34 control subjects from the same plant. Personal monitors were used to evaluate exposure to eight carcinogenic (polycyclic aromatic hydrocarbons) PAHs, including B[a]P, during an 8-h working shift. Smoking habits were checked by urinary cotinine measurement. The exposure among coke oven workers ranged widely from 0.6 to 547 microgram/m3 and 2 to 50 137 ng/m3, for carcinogenic PAHs and B[a]P, respectively. The respective values in controls were 0.07 to 1.51 microgram/m3 and from 2 to 63 ng/m3. The results of biomonitoring in exposed vs. control subjects were as follows: frequency of chromosomal aberrations (% AB.C.), 2. 30% AB.C. vs. 1.09% AB.C. (P<0.05); sister chromatid exchanges, 7.47 SCE/cell vs. 5.49 SCE/cell (P<0.05); HFC, 5.94% vs. 2.06% (P<0.05) and SCE-H index, 1.49 vs. 1.01 (P<0.05). All the cytogenetic markers were significantly increased in the exposed vs. control groups. The effect of smoking was observed only in SCE when evaluated as HFC. Using individual exposure data for carcinogenic PAHs, a significant correlation between exposure and %AB.C. (r=0.372, P=0.0002), SCE/cell (r=0.331, P=0.001), HFC (r=0.467, P=0.007) and SCE/H (r=0. 286, P=0.004) was found. No effects of GSTM1 and NAT2 genotypes, individually or in combination, on the cytogenetic markers was observed. It is concluded that occupational exposure of coke oven workers involved in this study resulted in an increased level of chromosomal aberrations and SCE. The frequency of AB.C. and SCE/cell was found to be related to exposure to carcinogenic PAHs.

Arylamine N-Acetyltransferase↗

PubMed1998

Cytogenetic study of buffalo under pollution of environmental conditions.

Thirty-four buffalos were used in the present study. Animals were kept in three experimental groups, two groups of which were reared in polluted areas, and the third group in an agricultural area (control group). the first and second groups were exposed to industrial and automobile exhaust emissions of genotoxic agents. Comparative cytogenetic analysis was made between the three groups. The cytogenetic studies of peripheral blood lymphocytes included chromosomal aberration and sister chromatide exchange (SCE). Significant differences (P<0.05) were observed in the percentage of cells with total chromosomal aberrations and gaps between buffalo from polluted and agricultural areas (31+/-1.4% and 21.1+/-6.7% and 7.6+/-1.6% and 6.8+/-1%, respectively). The differences of frequencies of the total gaps between the first and second groups were significant, while it was non-significant in the total chromosomal aberrations. The frequency of sister chromatide exchange of buffalo from polluted areas was 11.8+/-1.4% compared to 8.3+/-1. 2% from the agricultural area, the difference was statistically significant (P<0.05). These results indicated that cytogenetic analysis of chromosomes in peripheral lymphocytes of buffalo exposed to environmental pollution allows to direct detection of mutation in somatic cell, which can be prevented.

Agriculture↗

PubMed2004

Cytogenetic and sequence comparison of adult Phyllodistomum (Digenea: Gorgoderidae) from the three-spined stickleback with larvae from two bivalves.

Due to the low informative value of available morphological characters, cytogenetic and molecular methods, based on rDNA sequencing, were used to characterize adult and larval stages of Phyllodistomum spp. Species studied have 18 chromosomes with comparable absolute and relative lengths. Conventional Giemsa staining and karyometric analysis revealed clear differences in chromosome morphology of larval Phyllodistomum spp. infecting two bivalve host species, Sphaerium corneum and Pisidium amnicum. However, karyotypes of adult P. folium from three-spined sticklebacks and larval stages from S. corneum appear almost identical both with respect to the relative lengths and centromeric indices of the corresponding chromosome pairs. The entire internal transcribed spacer (ITS) region (ITS-1, 5.8S and ITS-2) and the D1-D3 region of 28S gene were sequenced and compared. Again, sufficient differences were observed between larval Phyllodistomum spp., while adult P. folium and larvae from S. corneum showed a high level of similarity. So, both cytogenetic and molecular data support the suggestion that they represent developmental stages of the same species. The results were compared with published data obtained by cytogenetic and molecular studies on the other Phyllodistomum species. Differences revealed in karyotype and rDNA sequences leads to the conclusion that the cercariaeum of P. folium sensu Sinitsin, 1905 could not be regarded as the larva of adult P. folium from three-spined stickleback.

Animals↗

PubMed1999

Cytogenetic analyses of secondary liver tumors reveal significant differences in genomic imbalances between primary and metastatic colon carcinomas.

To investigate if karyotypic features of secondary liver tumors may provide diagnostic information and if the cytogenetic patterns of primary and metastatic colorectal carcinomas (CRC) are different, 33 liver metastases were analyzed: 25 CRC, 4 small intestine carcinoids, 1 ovarian carcinoid, 1 lobular breast cancer, 1 head-and-neck squamous cell carcinoma, and 1 uveal malignant melanoma. Chromosomal aberrations were detected in 24 cases, whereas 5 had normal karyotypes and 4 were uninformative due to lack of mitoses. Trisomy 12 was detected in 2 small intestine carcinoids, suggesting that +12 may be of pathogenetic importance in this tumor type. The breast and head-and-neck carcinomas and the uveal melanoma displayed aberrations previously reported as characteristic in primary tumors, e.g., der(1;16) and deletion of 3p in the breast cancer, losses of 3p and 8p and partial gain of 8q in the head-and-neck carcinoma, and monosomy 3 and i(8)(q10) in the uveal melanoma, indicating that cytogenetic investigations provide important diagnostic information in secondary liver tumors. In the 18 CRC metastases with chromosomal abnormalities, the cytogenetic findings agreed well with previously reported primary CRC. Common numerical abnormalities included gains of chromosomes 7, 11, 13, and 20, and losses of Y, 4, 18, 21, and 22. Structural rearrangements most often affected chromosome bands 1p13, 1q10, 3p21, 5q10, 5q11, 7q10, 8q10, 8q11, 12q13, 16p13, 17p11, 20p13, 20p11, and 20q10, and frequently resulted in losses of 1p, 8p, and 17p, and gains of 5p, 6p, 7p, 8q, and 20q. Comparing the present cases with primary CRC previously analyzed in our department revealed that additional gains of 6p, 6q, 7p, and 20q, and losses of 1p, 4p, 4q, 8p, 18p, 18q, and 22 were more common (P < 0.05) in the metastases, suggesting that these genomic sites harbor genes of importance in the metastatic process of CRC.

Adult↗

PubMed1998

In vivo cytogenetic studies of the genotoxic effects of polymethyl methacrylate employed in orthopaedics.

Polymethyl methacrylate (PMMA) is a material employed as a cement in prosthesis that has been found to induce cytogenetic damage in human lymphocytes in vitro. This effect is particularly achieved before the 5th day of the exposition, while after this period no significant variations appeared. In the present study, results of cytogenetic tests in humans are reported. Sister chromatid exchange analysis and micronucleus tests have been performed on lymphocytes of patients who had undergone prosthesization with cemented prosthesis (group A) or with biological anchorage prosthesis, as control (group B). DNA damage was investigated before implantation and 5 d after surgery in both groups. Cytogenetic tests did not show any significant increase in the number of micronuclei and sister chromatid exchanges with respect to control values in patients with PMMA cemented prosthesis.

Journal Article↗

PubMed2001

Classical and molecular cytogenetics of the zebrafish, Danio rerio (Cyprinidae, Cypriniformes): an overview.

The zebrafish, Danio rerio, has recently become the model system for the genetic analysis of vertebrate development. This paper reviews the advances in zebrafish cytogenetics, obtained through classical and molecular techniques, which will lead to the assignment of specific linkage groups to specific chromosome pairs in the zebrafish genome project. Several chromosome pairs of the 50-chromosome karyotype of D. rerio were differentially stained by classical staining techniques and additional information has been obtained by molecular cytogenetics. Indeed, the analysis of constitutive heterochromatin by C-banding and base-specific fluorochrome staining had suggested a differential composition of peri- and paracentromeric constitutive heterochromatin. The chromosome mapping of distinct AT- and GC-rich zebrafish satellite DNAs by means of PRINS (Primed in situ) and multicolor FISH (Fluorescence in situ Hybridization) has confirmed this hypothesis, which therefore provided the chromosome localization of 10% of the zebrafish genome. The analysis of nucleolus organizer regions (NORs) by silver staining and by FISH with 18S rDNA has also revealed the existence of variable and inactive NORs, in addition to those on the terminal regions of the long arms of the three NOR-bearing chromosome pairs. Other multicopy genes, such as minor ribosomal genes, or multicopy repeats, such as telomere specific sequences, have now been mapped on zebrafish chromosomes. The latest advancement in zebrafish molecular cytogenetics is the chromosome mapping of single locus genes. Single-copy genes from each of the 25 genetic linkage groups are now being mapped on zebrafish chromosomes by using PAC clones.

Animals↗

PubMed2004

Flow cytogenetics and plant genome mapping.

The application of flow cytometry and sorting (flow cytogenetics) to plant chromosomes did not begin until the mid-1980s, having been delayed by difficulties in preparation of suspensions of intact chromosomes and discrimination of individual chromosome types. These problems have been overcome during the last ten years. So far, chromosome analysis and sorting has been reported in 17 species, including major legume and cereal crops. While chromosome classification by flow cytometry (flow karyotyping) may be used for quantitative detection of structural and numerical chromosome changes, chromosomes purified by flow sorting were found to be invaluable in a broad range of applications. These included physical mapping using PCR, high-resolution cytogenetic mapping using FISH and PRINS, production of recombinant DNA libraries, targeted isolation of markers, and protein analysis. A great potential is foreseen for the use of sorted chromosomes for construction of chromosome and chromosome-arm-specific BAC libraries, targeted isolation of low-copy (genic) sequences, high-throughput physical mapping of ESTs and other DNA sequences by hybridization to DNA arrays, and global characterization of chromosomal proteins using approaches of proteomics. This paper provides a comprehensive review of the methodology and application of flow cytogenetics, and assesses its potential for plant genome analysis.

Chromosomes, Plant↗

PubMed1996

Chromophilic renal cell carcinoma: cytomorphological and cytogenetic characterisation of four permanent cell lines.

Chromophilic renal cell carcinoma is a distinct type of human renal cancer, only recently recognised and defined by its characteristic histomorphological aspect and cytogenetic aberrations. We are the first to report on the establishment and cytogenetic characterisation of a panel of four permanent cell lines, i.e. chromphi-1, -2, -3 and -4, derived from strictly defined renal cell carcinomas (RCCs) of the chromophilic type and kept in continuous culture for up to 5 years. Immunohistochemistry revealed coexpression of vimentin and cytokeratins in all cell lines the cytokeratin polypeptide patterns, however, varying between the different cell lines. By light and transmission electron microscopy, various amounts of cytoplasmatic glycogen deposition were observed, being most pronounced in chromphi-3 and -4. The mean population doubling time ranged from 24 h (chromphi-1) to 51 h (chromphi-4). Chromphi-1 tumour cells produced slowly growing tumours in nude mice using the subrenal capsule assay. In all cell lines, cytogenetic analysis revealed numerical chromosomal aberrations known to be characteristic for chromophilic RCCs, i.e. loss of the Y chromosome, tri- or tetrasomy of chromosomes 7 and 17 as well as various combinations of additional structural and numerical chromosomal aberrations. Karyological aberrations were least pronounced in chromphi-2 and most complex in chromphi-1. Chromosomal aberrations typically affecting the short arm of chromosome 3 in clear cell RCCs were not observed in any of our cell lines.

Aged↗

PubMed1998

Cytogenetic and molecular genetic demonstration of polyclonality in an acinic cell carcinoma.

The paradigm that human malignancies are monoclonal has been questioned during recent years by the finding of unrelated, cytogenetically aberrant clones in short-term cultures from certain tumour types, notably carcinomas of the breast, skin and upper aerodigestive tract. In order to analyse whether cytogenetically unrelated clones are also unrelated at the molecular level, we analysed the X-chromosome inactivation status in cell cultures from a cytogenetically highly polyclonal acinic cell carcinoma of the parotid gland. By using cell cultures dominated by a single abnormal clone, obtained through in vitro culturing for 3-5 passages, we showed that the different clones must indeed have originated from different cells.

Aged↗

PubMed1995

Cytogenetic peculiarities in the Algerian hedgehog: silver stains not only NORs but also heterochromatic blocks.

Hedgehogs belong to one of the several mammalian taxa in which karyotype differences are based on variations in heterochromatin content. Furthermore, the number and location of nucleolar organizer regions (NORs) can also vary widely. In the present study these cytogenetic features were investigated in the Algerian hedgehog, Erinaceus (Aethechinus) algirus. The heterochromatin and NOR distribution patterns in the karyotype of this species are new among hedgehogs, whereas the euchromatic regions, including their G-band pattern, are similar to those reported by others. In addition, silver staining revealed a cytogenetic feature exclusive to the heterochromatic blocks of E. algirus: their silver staining with standard cytogenetic procedures. Because no similar phenomenon has been described previously in a mammalian species, several hypotheses about the significance and specificity of silver staining to NOR sites are discussed. Finally, the existence of different types of heterochromatin in the species analysed here, lead us to propose that what hedgehogs have inherited from their common ancestor is a mechanism which permits the accumulation of heterochromatin on specific chromosomes, rather than the heterochromatin itself.

Animals↗

PubMed2000

Autologous transplantation with Philadelphia-negative progenitor cells for patients with chronic myeloid leukaemia (CML) failing to attain a cytogenetic response to alpha interferon.

Between October 1993 and March 1999, 29 patients with CML who were ineligible for allogeneic BMT underwent PBSC harvest using idarubicin, cytarabine and G-CSF. In 9/29 (31%) patients all collected stem cells were Ph-negative, and 15/29 patients' (52%) collections were substantially (>95%) Ph-negative. The proportion of patients from whom Ph-negative stem cells were obtained was similar between patients who had, or had not, received prior alphaIFN. Fifteen patients in chronic phase (median age 45) proceeded to PBSCT following busulphan 16 mg/m2 and cyclophosphamide 120 mg/m2. Nine of the 13 patients who had failed to respond to prior alphaIFN proceeded to stem cell transplantation as soon as was feasible and six of the newly diagnosed patients were transplanted after failing to achieve a cytogenetic response after a minimum of 12 months on alphaIFN following progenitor cell harvest. The median number of days to neutrophils >0.5 and platelet >50 was 18 (range 13-69) and 28 (range 13-234), respectively. There was no procedure-related mortality. At median follow-up of 2.3 years post autograft 10 of 15 patients remain alive and in chronic phase. Overall survival for all 27 patients at 5 years after initial diagnosis is 70% and median survival from diagnosis 7.3 years. Survival for alphaIFN non-responders who were transplanted is 74% at 5 years from diagnosis and 75% at 3 years from transplant. Cytogenetic analysis performed 3 months post transplant demonstrated one patient with a complete cytogenetic response, seven with a partial response and three with no response. Six patients remain partially Ph-negative, with one major CR. Survival for all patients in the protocol is favourable compared with conventional therapy and is particularly encouraging following PBSCT for alphaIFN non-responsive patients. Patients not responding to alphaIFN can be induced into Ph-negativity with PBSCT but this may not always be sustainable. There seems to be no obvious disadvantage in harvesting stem cells after prior exposure to alphaIFN, providing an adequate alphaIFN-free rest period is used.

Adult↗

PubMed2004

Cytogenetic clonal evolution alone in CML relapse post-transplantation does not adversely affect response to imatinib mesylate treatment.

Good prognosis after imatinib mesylate treatment has been reported if cytogenetic clonal evolution (CE) is the only criterion of accelerated phase (AP) chronic myelogenous leukemia (CML). To evaluate the impact of CE upon imatinib treatment in post-transplant settings, responses and toxicities in the relapsed AP-CE were analyzed in comparison with those in the relapsed chronic phase (CP). Both CP (n=7) and AP-CE patients (n=6) received imatinib mesylate in an oral dose of 400 mg/day. Complete cytogenetic responses were obtained in six patients of each group, CP (86%) and AC-CE (100%), while molecular remission was seen in 43 and 50%, respectively. Granulocytopenia or thrombocytopenia of grade III or more occurred in four (57%) and two (33%) patients with CP and AP-CE, respectively. Nonhematological adverse events were mild and tolerable in both groups and only one (7%) of the 13 patients experienced recurrent graft-versus-host disease after imatinib treatment. Although this is a relatively small group of patients, we suggest that imatinib mesylate should be considered as a front-line treatment for relapsed CML as it showed the high response rate and low toxicity. We also suggest that CE alone is not an important factor in the induction of cytogenetic and molecular remissions in post-transplant relapse.

Adult↗

PubMed1997

Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma.

Malignant lymphomas often have complex, nonrandom chromosomal abnormalities. Hepatosplenic gammadelta T cell lymphoma (gammadelta TCL) is an unusual post-thymic T cell lymphoma that primarily involves liver and spleen, often in young adult males. Few cases have had cytogenetic analysis. We report a consistent isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gammadelta TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-, 37- and 65-year-old males, presented with hepatosplenomegaly and fevers. Histopathologic, immunophenotypic, and molecular genetic studies supported the diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic analysis of bone marrow showed i(7q) as the sole abnormality at presentation in one case. The second case showed i(7q) in addition to two normal chromosomes 7, and other structural and numerical abnormalities. The third case showed i(7q) and a deletion in the long arm of chromosome 11. These findings support the proposal that i(7q) represents the primary nonrandom cytogenetic abnormality in hepatosplenic gammadelta TCL, and plays a role in its pathogenesis.

Adolescent↗

PubMed1998

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.

We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that MM could correspond to two closely related diseases.

Adult↗

PubMed1999

Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia.

The t(12;21)(p13;q22) is a cryptic abnormality observed in 25% of children with B-lineage acute lymphoblastic leukemia (ALL), associated with a favorable prognosis. To determine whether specific cytogenetic abnormalities accompany the t(12;21), we analyzed the cytogenetic profiles of blast cells from 169 ALL cases positive for the t(12;21), previously identified by molecular methods. Only 13.6% of samples had normal karyotypes. Structural changes were detected in 89.7% of abnormal karyotypes, and numerical abnormalities in 47%. Rearrangements of 12p were the most frequent structural aberration (57 out of 146 patients with chromosomal abnormalities). Nonspecific deletions of chromosomes 6 and 9 were also found. The most frequent numerical abnormalities was trisomy for chromosomes 21. Blast cells were pseudodiploid (45.6%), hyperdiploid with 47 to 51 chromosomes (24.3%), hypodiploid with 44 to 45 chromosomes (10%), near-triploid (0.6%), or near-tetraploid (5.9%). Our results show that the t(12;21) is not associated with hyperdiploidy of 52 to 68 chromosomes or with the prognostic t(1;19), t(4;11) or t(9;22). Only children with B-lineage ALL who lack these abnormalities detected by conventional cytogenetics will probably benefit from additional testing by molecular methods to detect the t(12;21).

Child↗

PubMed1999

Cytogenetic analysis of the bipotential murine pre-B cell lymphoma, P388, and its derivative macrophage-like tumor, P388D1, using SKY and CGH.

Spectral karyotyping (SKY) and comparative genomic hybridization (CGH) were used to elucidate the divergent cytogenetic make-up of the prototypical bilineage lymphoblastic pre-B lymphoma, P388, and its progenitor macrophage-like tumor, P388D1. P388 was found to be diploid and genomically stable. P388D1 was triploid, highly unstable and characterized by numerous marker chromosomes (Chrs) and composite rearrangements. The karyotype of P388D1 was so complex that its clonal relatedness to P388 would have remained questionable without confirmation by molecular analysis of the clonotypic immunoglobulin heavy-chain and light-chain gene recombinations that coexisted in both tumors. The intrinsic instability of the P388D1 genome was indicated by the observation that only four out of 42 aberrations uncovered by SKY (in a total of 27 metaphases) occurred consistently (100% incidence), whereas 27 changes occurred non-randomly (27 to 96% incidence) and 11 alterations randomly (4 to 11% incidence). Persistent cytogenetic instability was also observed in P388 'macrophages' after phorbol ester- and ionomycin-induced conversion in vitro of P388 lymphoma cells. The 'cytogenetic noise' in these cells was manifested by a multiplicity of sporadic chromosomal aberrations; ie 25 distinct changes were identified by SKY in 40 metaphases. The results in P388D1 and P388 'macrophages' were interpreted to indicate that the myeloid differentiation program in the bipotential pre-B cell lymphoma P388 is invariably characterized by karyotypic instability. The study presented here demonstrates the power of the combined SKY and CGH approach to resolve complicated karyotypes of important and widely used mouse tumors.

Animals↗