Telomeric association in a malignant fibrous histiocytoma

Summary In a malignant soft-tissue fibrous histiocytoma 50–56 chromosomes were found in the majority of the metaphases. The most frequent numerical aberrations were one or two extra copies of chromosomes 4, 5, 18, 20, 22, and a missing chromosome 15. Structural rearrangements encountered were 11p+ and 1–5 unidentifiable markers. The most conspicuous feature was pairs of chromosomes intimately associated or fused at their telomeres, observed in 20 out of 22 metaphases. Although the telomeres of 6p, 11p, 16q, 20q, and 21p were involved most frequently, no preferential pattern of associations was detectable. This peculiar chromosomal behavior is compared to similar observations recently reported in a case of a B-cell lymphoid leukemia.     

Phenomenon of evolution of clonal chromosomal abnormalities in childhood acute myeloid leukemia

An analysis of chromosomal abnormalities in bone-marrow cells was performed in 116 children with diagnoses of acute myeloid leukemia (AML). The frequency of the evolution of clonal chromosomal abnormalities in AML constituted 42.3%. Quantitative abnormalities of chromosomes 8, 9, and 21, as well as the secondary structural abnormalities in the chromosomal regions 12p12, 9p22, 9q22, 9q34, 11q14–23, and 6q2, were the most abundant. Quantitative abnormalities were registered in 26.7% cases. The basic mechanism of evolution of the leukemic clone contained trisomy, deletions, and monosomy. The frequency of evolution was seven times higher in the age group of up to 2 years and twofold higher in the age group of up to 5 years. The high frequency of evolution at t(15;17)(q22;q22) was established, while its absence was revealed at inv(16)(p13q22). Patients with clonal evolution were characterized by the increased frequency of relapses and earlier death before reaching remission, which might be explained by the severe initial state of those patients. The conception of abnormalities in the evolution of the clone was proposed to occur at certain stages as follows: (1) appearance of balanced rearrangements; (2) trisomy occurrence; (3) loss of chromosomal material. The occurrence of an unbalanced genome during evolution possesses advantages in the clonal proliferate activity and may be related to its response to chemotherapy. An identity in abnormal chromosomal structure was revealed as a result of the comparison of karyotypes during diagnostics and during relapse, which could be evidence of the initial induction of some types of evolution of chromosomal abnormalities in leukemic cells in AML children by the chemical agents.     

Silver staining in clinical cytogenetics

Silver staining of human chromosomes at prometaphase or metaphase identifies variants in the stalk (nucleolar organizing) regions of acrocentric chromosomes (Nos. 13, 14, 15, 21, 22). Variants are defined by size, number, and morphology of silver staining areas. They are heritable polymorphisms and have not been associated with clinical abnormalities. However, these variants are useful in clinical cytogenetics, specifically in studies attempting to determine whether genetic material has been gained or lost in chromosomal rearrangements, the origin of chromosomal aberrations, the origin of cells in tissue culture, the chromosomal location of single genes, clonal origin of tumors, the zygosity of twins, and paternity. Some chromosomal aberrations require silver staining for their definition. Because loss of the stalk regions per se is apparently not deleterious, demonstration that chromosomal breaks occurred within this region without concomitant loss or gain of genetic material essential for normal human development provides basis for a good prognosis for the individual with the chromosomal rearrangement resulting from such breakage. The principle underlying most of the other applications is to determine whether variants being compared are identical or dissimilar, and to make inferences from these results (e.g., variants in monozygotic twins should all be identical, whereas in dizygotic twins they are as similar as in any pair of sibs). Silver staining is a valuable technique for special questions in clinical analysis.     

Distinct Genetic Alterations in Colorectal Cancer

Background

Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities.

Methodology/Principal Findings

We applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations.

Conclusions/Significance

Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.     

Silver Staining in Clinical Cytogenetics

Silver staining of human chromosomes at prometaphase or metaphase identifies variants in the stalk (nucleolar organizing) regions of acrocentric chromosomes (Nos. 13, 14, 15, 21, 22). Variants are defined by size, number, and morphology of silver staining areas. They are heritable polymorphisms and have not been associated with clinical abnormalities. However, these variants are useful in clinical cytogenetics, specifically in studies attempting to determine 1) whether genetic material has been gained or lost in chromosomal rearrangements, 2) the origin of chromosomal aberrations, 3) the origin of cells in tissue culture, 4) the chromosomal location of single genes, 5) clonal origin of tumors, 6) the zygosity of twins, and 7) paternity. Some chromosomal aberrations require silver staining for their definition. Because loss of the stalk regions per se is apparently not deleterious, demonstration that chromosomal breaks occurred within this region without concomitant loss or gain of genetic material essential for normal human development provides basis for a good prognosis for the individual with the chromosomal rearrangement resulting from such breakage. The principle underlying most of the other applications is to determine whether variants being compared are identical or dissimilar, and to make inferences from these results (e.g., variants in monozygotic twins should all be identical, whereas in dizygotic twins they are as similar as in any pair of sibs). Silver staining is a valuable technique for special questions in clinical analysis.     

SV40 T antigen induced chromosomal changes reflect a process that is both clastogenic and aneuploidogenic and is ongoing throughout neoplastic progression of human fibroblasts.

In human fibroblasts, the expression of SV40 large T antigen is known to cause a variety of chromosomal aberrations and especially dicentric chromosomes. In some cases, the later aberrations have been reported to be reversible telomeric associations. We report here aberration and chromosome number studies of twenty-nine T antigen positive lineages, studied from their initiation by transfection of T antigen sequences into human diploid fibroblasts, until crisis or immortalization occurred or, in some cases until the lines became tumorigenic in nude mice. The data show that T antigen consistently produced chromosomal instability of both number and structure by an active process that began before transformation indicators were positive and continued throughout neoplastic progression. The most frequently observed aberrations were dicentric chromosomes, which were shown to be true dicentrics by examination by in situ hybridization with telomeric sequences. These data are consistent with the hypothesis that T antigen causes human fibroblasts to become neoplastically transformed by successive rounds of chromosomal mutation and lineage evolution.     

Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: Fluorescence in situ hybridization and cytogenetic studies

Background: Chromosomal aberrations and instability of gene(s) are two factors related to the genetic instability of cancer cells. A loss of the tumor-suppressor function of the genes p16 and p53 is the most common event leading to the development of human cancers. Carcinoma of the lung is the leading cause of cancer deaths in the world. Chromosomal abnormalities in lung cancer may provide a valuable clue to the identification of target loci and culminate in a successful search for the major genes. The aim of this study was to investigate (i) alterations of the p16 and p53 genes and (ii) chromosomal aberrations in patients with small cell and non-small cell lung cancer by fluorescence in situ hybridization (FISH) and cytogenetic studies. Methods: We carried out cytogenetic analysis by Giemsa-banding in 18 cases. FISH probes for the p16 and p53 genes were also used on interphase nuclei to screen the alterations in these genes in lung cancer (LC).Results: We observed a high frequency of losses of the p16 – in 8/18 (44%) – and p53 – in 7/18 (39%) – genes in the cases with LC. A total of 18 patients showed predominantly numerical and structural aberrations. Among these two types, structural aberrations predominated and usually consisted of deletions, breaks, and fragilities in various chromosomes. Both structural and numerical changes were observed in almost all patients. Chromosomes 3 and 1 were found to be most frequently involved in structural abnormalities, followed by chromosomes 6, 9, and 8. Autosomal aneuploidies were also observed to be the most frequent (chromosomes 22, 19, 18, 20, 9, and 17), followed by those of the X and Y chromosomes. The expression of fragile sites was also found to be significantly higher in seven chromosomal regions: 3p14, 1q21, 1q12, 6q26, 9q13, 8q22, and 8q24. Conclusion: Our data confirmed that DNA damage and genomic instability may be factors contributing to the mutation profile and development of lung cancer. The patients who developed lung cancer showed a high frequency of loss of both p16 and p53, in addition to chromosomal aberrations. Tobacco could be a major carcinogenic factor in lung-cancer progression. The loss of p16 and p53, and increased incidence of autosomal aneuploidy and chromatid breaks, along with other chromosomal alterations, can contribute to the progression of the disease.     

Chromosomal aberrations in foreign body tumorigenesis of mice

Sarcomas were induced in 107 male and female isogeneic CBA/H or CBA/H-T6 mice by subcutaneous implantation of double films of unplasticized vinylchloride-acetate copolymer, 15 x 22 x 0.2 mm in size. Tumors were grouped by chromosome number. G-banding was performed on chromosomes of (a) 12 sarcomas, (b) 6 specimens of preneoplastic cells derived from foreign body (FB)-reactive tissues at 4, 6, 9, and 16 months postimplantation, and (c) 11 sarcomas which developed from clonal lines of the preneoplastic cells studied. Karyological analyses lead to the following results and conclusions: (1) Various derangements in chromosome number occurred in preneoplastic cells during early FB reaction at the time of, and possibly in causal relation to carcinogenic initiation. (2) Structural abnormalities of specific chromosomes (insertions, translocations, transpositions, etc.) were found as stable cell markers only during late preneoplasia. They may thus contribute to advanced tumor progression. (3) Ploidy deviations of specific chromosomes (secondary to the early derangements in chromosome number) were most frequently seen in chromosomes 1, 6, 7, 13, 15, 18, and 19; however, these latter aberrations were unstable and inconsistent both in vivo and in vitro.     

Multilocus genetic analysis of single interphase cells by spectral imaging

Numerical chromosome aberrations are detrimental to early embryonic, fetal and perinatal development of mammals. When fetuses carrying a chromosomal imbalance survive to term, an aberrant gene dosage typically leads to stillbirth or causes a severely altered phenotype. Aneuploidy of any of the 24 chromosomes will negatively impact on human development, and a preimplantation and prenatal genetic diagnosis test should thus score as many chromosomes as possible. Since cells available for analysis are likely to be in interphase, we set out to develop a rapid enumeration procedure based on hybridization of chromosome-specific probes and spectral imaging detection. The probe set was chosen to allow the simultaneous enumeration of ten chromosome types and was expected to detect more than 70% of all numerical chromosome aberrations responsible for spontaneous abortions, i.e., human chromosomes 9, 13, 14, 15, 16, 18, 21, 22, X, and Y. Cell fixation protocols were optimized to achieve the desired detection sensitivity and reproducibility. We were able to resolve and identify ten separate chromosomal signals in interphase nuclei from different types of cells, including lymphocytes, uncultured amniocytes, and blastomeres. In summary, this study demonstrates the strength of spectral imaging, allowing us to construct partial spectral imaging karyotypes for individual interphase cells by assessing the number of each of the target chromosome types.     

Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome painting

Fluorescence in situ hybridisation (FISH) technique with chromosome specific library (CSL) DNA probes for all human chromosomes were used to study about 9000 micronuclei (MN) in normal and idoxuridine (IUdR)-treated lymphocyte cultures of female and male donors. In addition, MN rates and structural chromosome aberrations were scored in Giemsa-stained chromosome spreads of these cultures. IUdR treatment (40 microg/ml) induced on the average a 12-fold increase of the MN rate. Metaphase analysis revealed no distinct increase of chromosome breaks but a preferential decondensation at chromosome 9q12 (28-79%) and to a lower extend at 1q12 (8-21%). Application of FISH technique with CSL probes to one male and one female untreated proband showed that all human chromosomes except chromosome 12 (and to a striking high frequency chromosomes 9, X and Y) occurred in spontaneous MN. In cultures containing IUdR, the chromosomal spectrum found in MN was reduced to 10 chromosomes in the male and 13 in the female proband. Eight chromosomes (2, 6, 12, 13, 14, 15, 17 and 18) did not occur in MN of both probands. On the contrary chromosomes 1 and especially 9 were found much more frequently in the MN of IUdR-treated cultures than in MN of control cultures. DAPI-staining revealed heterochromatin signals in most of the IUdR-induced MN. In an additional study, spontaneous and IUdR-induced MN were investigated in lymphocytes of another female donor using CSL probes only for chromosomes 1, 6, 9, 15, 16 and X. The results confirmed the previous finding that chromosomes 1 and 9 occur very often in MN after IUdR-treatment. The results indicate that decondensation of heterochromatic regions on chromosomes 1 and 9 caused by IUdR treatment strongly correlates with MN formation by these chromosomes.     

Chromosomal mosaicism in spontaneous abortions: Analysis of 650 cases

It is known that up to 50% spontaneous abortions (SA) in the first trimester of pregnancy are associated with chromosomal abnormalities. We studied mosaic forms of chromosomal abnormalities in 650 SA specimens using interphase MFISH and DNA probes for chromosomes 1, 9, 13/21, 14/22, 15, 16, 18, X, and Y. Numerical chromosomal abnormalities were discovered in 58.2% (378 cases). They contained combined chromosomal abnormalities (aneuploidy of several chromosomes or aneuploidy in combination with polyploidy in the same specimen) in 7.7% (29 cases) or 4.5% of the entire SA sample; autosomal trisomy, in 45% (18.2% in chromosome 16, 8.9% in chromosomes 14/22, 7.9% in chromosomes 13/21, 3.1% in chromosome 18, and 1.4% in chromosome 9). Chromosome X aneuploidy was found in 27% cases, among which 9.6% represented chromosome X monosomy. Polyploidy was observed in 22.9% cases. In 5.1% cases, we observed mosaic form of autosomal monosomy. Among the SA cases with chromosomal abnormalities mosaicism was observed in 50.3% (∼ 25% of the entire SA sample). The results of the present study indicate that significant amount of chromosomal abnormalities in SA cells are associated with disturbances in mitotic chromosome separation, which represents the most common cause of intrauterine fetal death. It was also shown that original collection of DNA probes and the technique of interphase MFISH could be useful for detection of chromosomal mosaicism in prenatal cell specimens.     

Induction of tumorigenesis and chromosomal abnormalities in human amniocytes infected with simian virus 40 and kirstein sarcoma virus

Summary Cell cultures of epithelial-like human amniocytes were infected with simian virus 40 (SV40) and Kirsten sarcoma virus (KSV) in various sequential orders, and tested for agar growth, chromosome abnormalities, and tumorigenesis in the nude mouse assay. We observed that regardless of the order in which the viruses were introduced, the doubly infected cells always exhibited the typical SV40 premalignantly transformed phenotype before changing to the malignant phenotype. All doubly transformed cells from different cell donors produced tumors in adult and suckling nude athymic mice, classified as poorly differentiated sarcomas. Infection with SV40 alone conferred extended life span and accelerated growth without, the malignant capability of tumor production. Kirsten sarcoma virus alone produced only focal cell alteration with no change in cell longevity or tumorigenesis. Chromosome studies of the premalignant and malignant cells from one cell donor did not reveal any significant clonal development for marker chromosomes in either cell line. Chromosome 12, which carries the homologous cellular oncogene to KSV, had no increase in aberrations in the malignant cells. Chromosome 8 was most often involved in aberrations, and the most frequent aberration for both series was dicentric chromosomes due to telomere fusion. For other translocations the breakpoints were almost exclusively in the centromere regions. The vulnerability of telomere and centromere regions to the free virus present in these precrisis cells is discussed, and similarities in regard to types of aberrations in transfection experiments are noted.     

Significance of inherited fragile sites in the occurrence of chromosome aberrations in tumor cells

The data on localization of heritable fragile sites and cellular oncogenes on individual human chromosomes involved in tumour-specific aberrations are summarized in the review. Only two fragile sites (8q22 and 11q13) out of eight ones, coinciding with breakage sites in such aberrations are the loci of cellular oncogenes (mos and bcl-1, respectively). Analysis of the data confirms the supposition that heritable fragile sites are predisposing factors for chromosomal rearrangements and in the end for development of the pathological processes.     

Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome painting

Fluorescence in situ hybridisation (FISH) technique with chromosome specific library (CSL) DNA probes for all human chromosomes were used to study about 9000 micronuclei (MN) in normal and idoxuridine (IUdR)-treated lymphocyte cultures of female and male donors. In addition, MN rates and structural chromosome aberrations were scored in Giemsa-stained chromosome spreads of these cultures. IUdR treatment (40 μg/ml) induced on the average a 12-fold increase of the MN rate. Metaphase analysis revealed no distinct increase of chromosome breaks but a preferential decondensation at chromosome 9q12 (28–79%) and to a lower extend at 1q12 (8–21%). Application of FISH technique with CSL probes to one male and one female untreated proband showed that all human chromosomes except chromosome 12 (and to a striking high frequency chromosomes 9, X and Y) occurred in spontaneous MN. In cultures containing IUdR, the chromosomal spectrum found in MN was reduced to 10 chromosomes in the male and 13 in the female proband. Eight chromosomes (2, 6, 12, 13, 14, 15, 17 and 18) did not occur in MN of both probands. On the contrary chromosomes 1 and especially 9 were found much more frequently in the MN of IUdR-treated cultures than in MN of control cultures. DAPI-staining revealed heterochromatin signals in most of the IUdR-induced MN. In an additional study, spontaneous and IUdR-induced MN were investigated in lymphocytes of another female donor using CSL probes only for chromosomes 1, 6, 9, 15, 16 and X. The results confirmed the previous finding that chromosomes 1 and 9 occur very often in MN after IUdR-treatment. The results indicate that decondensation of heterochromatic regions on chromosomes 1 and 9 caused by IUdR treatment strongly correlates with MN formation by these chromosomes.     

Clonal chromosome aberrations are present in vivo in synovia and osteophytes from patients with osteoarthritis

We have previously reported recurrent clonal chromosomal aberrations in synovia, osteophytes and articular cartilage from patients with osteoarthritis (OA). In particular, gain of chromosomes 5 and 7 was found to be strongly associated with OA. In order to exclude the possibility of in vitro artefacts, we studied three to four parallel, independent cultures from ten samples of synovia and three samples of osteophytes from ten women with primary OA. In all, 40 cultures were cytogenetically analysed, 39 of which had clonal chromosomal aberrations. The most common aberrations were +7 and +5 which were found in 38 and 12 cultures, respectively. There were striking karyotype similarities among the parallel cultures from each case. Out of a total of 83 clones, only 11 were unique for one culture, 7 from synovia and 4 from osteophytes. The genetic homogeneity among different cultures from the same patients excludes the possibility of in vitro artefacts and indicates a widespread distribution of the cytogenetically aberrant clones in vivo. Received: 16 July 1997 / Accepted: 25 August 1997     

16种罕见的人类染色体异常核型报告

通过对患有闭经、自发流产、死胎、死产等患者外周血淋巴细胞染色体检查,发现16种新的罕见人类染色体异常核型,它们是46,XY,t(6;11)(q25;p15);46,XY,inv(3)(p25;q29);46,XY,t(7;18)(q10;p10);46,X,t(X;13)(q24;q14);46,XY,t(4;7)(q33;q22);46,XY,t(8;15)(q24;q15);46,XY,t(2;17)(q33;q25);46,XX,t(4;7)(q34;q11);46,XX,t(1;3)(p36;p23);46,XX,t(4;6)(q35;p11);46,X,inv(X)(q22;q28);46,XX,t(7;10)(p11;q26);46,XX,t(3;6)(p21;q23);46,XX,t(8;16)(p21;p13);46,XX,t(8;9)(q21;q34);46,XY,t(17;22)(q21;q11)。描述了患者的临床表现,并对生殖异常患者染色体畸变与其表型效应关系进行探讨。Abstract：By examining the lymphocytic chromosomes of peripheral blood from patients with amenorrhea,spontaneous abortion and stillbirth history, .the 16 rare species of human chromosomal abnormal karyotypes were discovered. They wre 46,XY,t(6;11)(q25;p15);46,XY,inv(3)(p25;q29);46,XY,t(7;18)(q10;p10);46,X,t(X;13)(q24;q14);46,XY,t(4;7)(q33;q22);46,XY,t(8;15)(q24;q15);46,XY,t(2;17)(q33;q25);46,XX,t(4;7)(q34;q11);46,XX,t(1;3)(p36;p23);46,XX,t(4;6)(q35;p11);46,X,inv(X)(q22;q28);46,XX,t(7;10)(p11;q26);46,XX,t(3;6)(p21;q23);46,XX,t(8;16)(p21;p13);46,XX,t(8;9)(q21;q34);46,XY,t(17;22)(q21;q11). Their clinical situation were described. Discussion on the relationship between the chromosomal aberrations and phenotype effect indicates the importance of chromosome karyotyping in patients with abnormal reproductive history.     

Site-specific chromosomal rearrangements induced in human diploid cells by x-irradiation

A total of 130 stable, two-break reciprocal translocations were scored in G-banded karyotypes prepared from 375 metaphase spreads from a strain of human diploid fibroblasts irradiated with 400 or 600 rads and analyzed 1-20 mean population doublings later. The chromosomal location of each of the 260 breakpoints was mapped. The sites of 121 chromosomal breaks and deletions in the first postirradiation mitosis were also scored. Unlike the random distribution of these latter events, the translocation breakpoints showed not only a nonrandom distribution among chromosomes but also the existence of specific sites within chromosomes that were more frequently involved in translocations. The most notable finding was a marked excess of translocations involving the short arm of chromosome 1, in particular, band 1p22. The specific types of translocations were random, although the breakpoints were not. Eight of the 12 most frequently involved chromosomal sites were regions in which fragile sites have been mapped in human lymphocytes.     

The action of N-methyl-N-nitrosourea on non-established human cell lines in vitro. II. Non-random distribution of chromatid aberrations in diploid and Down's cells.

Chromatid gaps, breaks and aberrations involved in interchanges induced by N-methyl-N-nitrosourea (MNU) were found non-randomly distributed on individual chromosomes and chromosome segments (G bands) both in human diploid fibroblasts with trisomy 21 cultured in vitro. Aberration events were located exclusively in pale G bands. Considering cells in the first post-treatment mitosis, the pattern of aberration distribution, as revealed by the position of hot spots, varied with recovery time and was different in diploid and Down's cells. In comparison with diploid cells, the X chromosomes of Down's cells were not involved in aberrations. Despite the higher aberration frequencies of Down's cells, the number of hot spots and the proportion of aberrations located in hot spots were not increased in this cell type. Therefore, the increased chromosomal sensitivity to MNU of Down's cells does not reflect an increased sensitivity of special chromosomes or chromosome sites.     

Incidence of numerical chromosome aberrations in meningioma tumors as revealed by fluorescence in situ hybridization using 10 chromosome-specific probes

OBJECTIVE: Although information on the cytogenetic characteristics of meningioma tumors has accumulated progressively over the past few decades, information on the genetic heterogeneity of meningiomas is still scanty. The aim of the present study was to analyze by interphase fluorescence in situ hybridization (FISH) the incidence of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in a group of 70 consecutive meningioma tumors. Another goal was to establish the potential associations among the altered chromosomes, as a way to assess both intertumoral and intratumoral heterogeneity. METHODS: For the purpose of the study, 70 patients diagnosed with meningioma were analyzed. Interphase FISH for the detection of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y was applied to fresh tumor samples from each of the patients studied. RESULTS: The overall incidence of numerical abnormalities was 76%. Chromosome Y in males and chromosome 22 in the whole series were the most common abnormalities (46% and 61%, respectively). Despite the finding that monosomy of chromosome 22/22q(-) deletions are the most frequent individual abnormality (53%), we have observed that chromosome gains are significantly more common than chromosome losses (60% versus 40%). Chromosome gains corresponded to abnormalities of chromosomes 1 (27%), 9 (25%), 10 (23%), 11 (22%), 14 (33%), 15 (22%), 17 (23%), and X in females (35%) and males (23%) whereas chromosome losses apart from chromosome 22 frequently involved chromosomes 14 (19%), X in males (23%), and Y in males (32%). Although an association was found among most gained chromosomes on one side and chromosome losses on the other side, different association patterns were observed. Furthermore, in the latter group, monosomy 22/22q(-) was associated with monosomy X in females and monosomy 14/14q(-) was associated with nulisomy Y in males. In addition, chromosome losses usually involved a large proportion of the tumor cells whereas chromosome gains were restricted to small tumor cell clones, including tetraploid cells. CONCLUSIONS: Our results show that meningiomas are genetically heterogeneous tumors that display different patterns of numerical chromosome changes, as assessed by interphase FISH.