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Showing papers on "Karyotype published in 1994"


Journal ArticleDOI
15 May 1994-Blood
TL;DR: All of the most important chromosome aberrations found in de novo AML are now also found in therapy-related AML (t-AML); thus, t-AMl may serve as a model in the search for mechanisms leading to the development of AML in general.

340 citations


Journal Article
TL;DR: A specific combination of multiple chromosomal losses characterizes chromophobe renal cell carcinomas and may help to differentiate them unequivocally from other types of kidney cancer.
Abstract: We analyzed 19 chromophobe renal cell carcinomas by means of comparative genomic hybridization. Two tumors revealed no numerical abnormalities. In the remaining 17 cases we found loss of entire chromosomes with underrepresentation of chromosome 1 occurring in all 17 cases; loss of chromosomes 2, 10, and 13 in 16 cases; loss of chromosomes 6 and 21 in 15 tumors; and loss of chromosome 17 in 13 cases. The loss of the Y chromosome was observed in 6 of 13 tumors from male patients, whereas 1 X chromosome was lost in 3 of 4 tumors obtained from females. Comparative genomic hybridization results were verified by interphase cytogenetics. We conclude that a specific combination of multiple chromosomal losses characterizes chromophobe renal cell carcinomas and may help to differentiate them unequivocally from other types of kidney cancer.

288 citations


Book
01 Jan 1994

277 citations


Journal ArticleDOI
TL;DR: It is concluded that ZOO–FISH can be used to generate comparative chromosome maps of a large number of mammalian species.
Abstract: Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species.

275 citations


Journal ArticleDOI
TL;DR: There is accumulating evidence, particularly from flow cytometry and allelotype studies reviewed here, to suggest that the genetic evolution associated with tumor development and progression does reach a stage of equilibrium despite the presence of extensive tumor heterogeneity.

220 citations


Journal ArticleDOI
TL;DR: To begin to fathom the function of the extra abnormal chromosomes, the amplification of genes, including SAS, MDM2, and GADDI53/CHOP, known to be in the region 12q 13–14 were examined and SAS andMDM2 demonstrated constant co‐amplification.
Abstract: Extra abnormal chromosomes (rings and giant rods) containing chromosome 12 sequences are characteristic of well-differentiated liposarcoma (WDLPS). By whole chromosome painting we found in 6 WDLPS that minimally 5 chromosomes had contributed to the formation of the extra abnormal chromosomes. To the constant chromosome 12 contribution, sequences were variably added from chromosomes 1, 4, and 16. Material from chromosomes 1, 4, and 12 was identified by painting in interphase nuclear projections ("blebs") and in micronuclei consistent with the concept that blebs are precursors to micronuclei. The complexity of the mechanisms generating the extra abnormal chromosomes in WDLPS was also attested to by the diversity and, in some cases, intricacy of the patterns of fluorescence. To begin to fathom the function of the extra abnormal chromosomes we examined the amplification of genes, including SAS, MDM2, and GADD153/CHOP, known to be in the region 12q13-14. SAS and MDM2 demonstrated constant co-amplification. GADD153/CHOP, which is critically rearranged in myxoid liposarcoma, was not amplified in WDLPS.

182 citations


Journal Article
TL;DR: A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue.
Abstract: Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue.

171 citations


Journal ArticleDOI
TL;DR: Examination of clonality of 36 leiomyomata from 16 patients by analyzing X chromosome inactivation as indicated by the methylation status of the X‐linked androgen receptor gene suggests that karyotypically normal cells present in short‐term cultures of uterine leiomata are part of the tumor clone, and that clonal expansion of tumor cells precedes the development of cytogenetic aberrations.
Abstract: Uterine leiomyomata are thought to be monoclonal neoplasms. Accordingly, investigations of clonality with G6PD isoforms used as a marker for X chromosome inactivation have suggested independent origins for multiple tumors within individual uteri. However, results from a recent study assessing methylation differences between DNA of active and inactive X chromosomes have been interpreted to suggest that multiple tumors may arise from a common precursor. We have examined the clonality of 36 leiomyomata from 16 patients by analyzing X chromosome inactivation as indicated by the methylation status of the X-linked androgen receptor gene. As shown by this assay, all informative leiomyomata were monoclonal in origin. In patients with multiple leiomyomata, a random distribution of inactivation between the X homologs was noted, consistent with an independent origin of each tumor. Cytogenetic analysis was also performed on short-term cell cultures of 27 of the 36 tumors. In each of two tumors that had both cells with a clonal karyotypic abnormality and karyotypically normal cells, DNA prepared from short-term cultures showed a monoclonal pattern of X inactivation identical to that of the leiomyoma from which they were derived. These data suggest that karyotypically normal cells present in short-term cultures of uterine leiomyomata are part of the tumor clone, and that clonal expansion of tumor cells precedes the development of cytogenetic aberrations.

162 citations


Journal ArticleDOI
TL;DR: The data extend previous cytogenetic findings and suggest that, in addition to the known involvement of chromosome I, one or more genes on chromosome 17 also play a role in neuroblastoma development.
Abstract: We report on the finding of a t(1;17) in two primary neuroblastomas. Subsequent fluorescence in situ hybridization (FISH) analysis revealed the presence of 1; 17 transfocations in four out of nine neuroblastoma cell lines. The chromosome 1 short arm breakpoints were determined using region-specific probes. FISH screening also demonstrated or confirmed the presence of 11;17 translocations in three cell lines and other chromosome 17 rearrangements in those cell lines that did not carry a t(1; 17) or t(11; 17). Our data extend previous cytogenetic findings and suggest that, in addition to the known involvement of chromosome I, one or more genes on chromosome 17 also play a role in neuroblastoma development. Genes Chromosom Cancer 10:103–114 (1994). © 1994 Wiley-Liss, Inc.

140 citations


Journal ArticleDOI
TL;DR: The chromosome constitution of five haploid, 178 diploid and 11 triploid embryos fertilized in vitro was determined and the relative proportions of chromosomes involved in trisomic karyotypes showed a remarkable similarity to the pattern in spontaneous abortions.
Abstract: The chromosome constitution of five haploid, 178 diploid and 11 triploid embryos fertilized in vitro was determined after fixation on day 2 or day 3 of development. Karyotype analysis of 178 diploid embryos revealed abnormalities in 40 (22.5%) cases: 34 (19.1%) aneuploids, four (2.2%) mosaic embryos and two (1.1%) structural anomalies were identified. The majority of aneuploid karyotypes (28/34) involved a single chromosome but six embryos had aneuploidy of two or three chromosomes. The E group was most frequently involved in aneuploid karyotypes (10/23 hyperdiploid embryos) and trisomy 16, the most common single anomaly in diploid embryos, was detected in 2.2% (4/178) of cases. Only one case of sex chromosome monosomy was identified. An excess of female karyotypes was detected in abnormal cases (sex ratio 0.48); this ratio was significantly (P < 0.05) different from that observed in normal cases (74:64, XY:XX). The incidence of aneuploidy increased with maternal age but this did not reach statistical significance. Embryo morphology and growth rate, assessed by embryo development rating (EDR), did not distinguish between normal (mean score 7.9; mean EDR 96.1) and aneuploid (mean score 8.1; mean EDR, 92.1) embryos. Numbers of hyperploid (n = 17) and hypoploid (n = 11) embryos (non-mosaic cases involving single chromosomes) were not statistically different. The relative proportions of chromosomes involved in trisomic karyotypes showed a remarkable similarity to the pattern in spontaneous abortions. Pronuclear status was an unreliable predictor of ploidy. Small numbers of karyotyped triploid embryos revealed equal proportions of XXX, XXY and XYY embryos.

124 citations


Journal ArticleDOI
TL;DR: A complex chromosome rearrangement involving chromosomes 7, 8, and 13 was detected in a phenotypically normal woman ascertained through her mentally retarded son with abnormal phenotype and was interpreted as a three-way translocation and an insertion.
Abstract: A complex chromosome rearrangement (CCR) involving chromosomes 7, 8, and 13 was detected in a phenotypically normal woman ascertained through her mentally retarded son with abnormal phenotype. He had a karyotype with 47 chromosomes including an extra der(13). In initial banding studies the CCR in the mother was interpreted as a three-way translocation. Fluorescence in situ hybridization with whole chromosome libraries and a telomere-specific probe was used to better characterize the rearrangement. Combined data allowed us to reinterpret the CCR as a translocation and an insertion. A review of 35 familial CCRs involving at least three chromosomes led to the following observations: 1) familial CCRs tend to have fewer chromosomes involved and fewer break-points than do de novo CCRs; 2) familial transmission is mainly observed through female carriers although the origin of de novo cases is paternal; 3) an apparent excess of balanced female carriers among the offspring of index carriers was noted; and 4) meiotic segregation resulting in malformed liveborn infants is most frequently due to adjacent-1 segregation, followed by 4:2 segregation; no adjacent-2 segregation was observed.

Journal ArticleDOI
TL;DR: Karyotypic diversity was the highest in Iraq followed by Transcaucasia and Turkey, and Iraq should be considered as a centre of origin and primary centre of diversity ofT.
Abstract: Karyotypes of 185 accessions ofTriticum araraticumJakubz. (2n = 28 = 4x = AtAtGG) from Iraq, Iran, Turkey, and Transcaucasia were analyzed using C-banding technique. All accessions showed a certain degree of C-banding polymorphism and further karyotypic diversity was generated by structural rearrangements, mainly translocations. Eighty-one accessions had the normal karyotype similar to that ofT. timopheevii (cultivation), i.e., they showed C-banding polymorphism but no chromosomal rearrangements based on the resolving power of the C-banding technique. One-hundred four accessions showed 34 karyotypic variants, 31 had reciprocal translocations with the breakpoints in the centromeric regions of chromosomes. Three showed reciprocal translocations with the breakpoints in intercalary regions of chromosomes. A paracentric inversion for 7At chromosome was observed in some accessions. The rearranged karyotypes differed from the normal by one translocation in 21 variants, by two in 9 variants, by three in 1 variant, and by four in 2 variants of karyotypes. Translocations occurred more frequenty in the chromosomes of G-genome than of At-genome. Individual chromosomes differed in the frequencies of their involvement in translocations. Each geographical region contained a unique spectrum of translocations. Karyotypic diversity was the highest in Iraq followed by Transcaucasia and Turkey. Iran showed little karyotypic variation. Based on karyotypic analysis, Iraq should be considered as a centre of origin and primary centre of diversity ofT. araraticum.

Journal Article
TL;DR: This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype.
Abstract: Twenty-seven cases of inverted duplications of chromosome 15 (inv dup [15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P < .01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype.

Journal Article
TL;DR: It is reported that the deleted 1p material in cells of neuroblastoma lines is preferentially replaced by material from chromosome 17, resulting from an unbalanced 1;17 translocation.
Abstract: Human neuroblastoma cells often are monosomic for the distal portion of 1p (1p36). The authors report that the deleted 1p material in cells of neuroblastoma lines is preferentially replaced by material from chromosome 17, resulting from an unbalanced 1;17 translocation. Chromosome 17 often acquires instability, followed by the integration of fragments into various marker chromosomes. As a consequence, 17q material can increase over 17p material. The nonrandom frequency of 1;17 translocations appears to indicate an as-yet-undefined contribution to neuroblastoma development. 35 refs., 4 figs., 1 tab.

Journal ArticleDOI
TL;DR: The aim of this study was to see if the classification of XX sex‐reversed individuals into three groups, Y‐DNA‐positive phenotypically normal XX males, Y-DNA‐negative XX males with genital ambiguities and Y‐ DNA‐negative true hermaphrodites can be applied to cases.
Abstract: OBJECTIVE Testicular differentiation can occur in the absence of the Y chromosome giving XX sex-reversed males. Although Y chromosomal sequences can be detected in the majority of male subjects with a 46,XX karyotype, several studies have shown that approximately 10% of patients lack Y material including the SRY gene. The aim of this study was to see if the classification of XX sex-reversed individuals into three groups, Y-DNA-positive phenotypically normal XX males, Y-DNA-negative XX males with genital ambiguities and Y-DNA-negative true hermaphrodites can be applied to our cases. DESIGN Endocrinological and genetic studies were conducted in 20 XX sex-reversed patients. PATIENTS Twenty patients with various phenotypes were studied. They were between 20 days and 35 years old. Ten presented ambiguous external genitalia (Prader's stages II to IV). After laparotomy or gonadal biopsy, the diagnosis was 46,XX true hermaphroditism in five, and XX male in 15. MEASUREMENTS Blood samples were obtained from all patients for hormonal and molecular studies. Basal levels of testosterone, oestradiol and pituitary gonadotrophins were measured by RIA. In addition, two stimulation tests were performed: gonadotrophin stimulation with GnRH and testicular stimulation with hCG. Several Y-specific DNA sequences of the short arm of the Y chromosome were analysed by Southern blot and polymerase chain reaction methods. RESULTS In this study, three categories of XX sex-reversed individuals were observed: phenotypically normal males with or without gynaecomastia, males with genital ambiguities, and true hermaphrodites. Endocrinological data were similar in XX males and in true hermaphrodites. Testosterone levels exhibited normal (n = 9) or decreased (n = 11) values. The hCG response was low. FSH and LH were elevated in 13 patients. Molecular analysis in ten patients showed varying amounts of Y material including the Y boundary and SRY. Ten patients with various phenotypes lacked Y chromosomal DNA. There was no relation between Leydig cell function (as indicated by testosterone levels before or after hCG stimulation) and the presence of Y chromosome material. CONCLUSION Although the presence of Y-specific DNA generally results in a more masculinized phenotype, exceptions do occur. In the Y-DNA-negative group, complete or incomplete masculinization in the absence of SRY suggests a mutation of one or more downstream non-Y, testis-determining genes.

Book ChapterDOI
TL;DR: One of the major technical breakthroughs in Drosophila mitotic cytology will be the development of fixation procedures that maximize chromosomal quality with minimal removal of proteins.
Abstract: The repertoire of cytological procedures described in the present paper permits full analysis of brain neuroblast chromosomes Moreover, if brains are cultured for 13 hr in the presence of 5-bromo-2'-deoxy-uridine, our fixation and Hoechst staining protocols allow visualization of sister chromatid differentiation and the scoring of sister chromatid exchanges (Gatti et al, 1979) Finally, we note that our cytological procedures can be successfully employed for preparation and staining of gonial cells of both sexes and male meiotic chromosomes (Ripoll et al, 1985; our unpublished results) Good chromosome preparations of female meiosis are obtained with the procedure described by Davring and Sunner (1977, 1979), Nokkala and Puro (1976), and Puro and Nokkala (1977) In this chapter, we have focused on the organization and behavior of Drosophila mitotic chromosomes, describing a repertoire of cytological techniques for neuroblast chromosome preparations We have not considered the numerous excellent cytological procedures for embryonic chromosome preparations (for an example, see Foe and Alberts, 1985; Foe, 1989), because these chromosomes are usually less clearly defined than those of larval neuroblasts In addition, we have not included the whole-mount and squashing techniques that allow chromosome visualization and spindle immunostaining of neuroblast cells (Axton et al, 1990; Gonzalez et al, 1990), male meiotic cells (Casal et al 1990; Cenci et al, 1994), and female meiotic cells (Theurkauf and Hawley 1992), because the fixation methods used in these procedures alter chromosome morphology Fixation methods for antibody staining result in poorly defined chromosomes, whereas the methanol/acetic acid fixation techniques, such as those described here, preserve very well chromosome morphology but remove a substantial fraction of chromosomal proteins Thus, one of the major technical breakthroughs in Drosophila mitotic cytology will be the development of fixation procedures that maximize chromosomal quality with minimal removal of proteins This will be particularly useful for precise immunolocalization of heterochromatic proteins, including those associated with the centromere

Journal ArticleDOI
TL;DR: It is proposed that at least one of the genes (SEN6) for cellular senescence in human fibroblasts is present on the long arm of chromosome 6.
Abstract: In these studies we show that introduction of a normal human chromosome 6 or 6q can suppress the immortal phenotype of simian virus 40-transformed human fibroblasts (SV/HF). Normal human fibroblasts have a limited life span in culture. Immortal clones of SV/HF displayed nonrandom rearrangements in chromosome 6. Single human chromosomes present in mouse/human monochromosomal hybrids were introduced into SV/HF via microcell fusion and maintained by selection for a dominant selectable marker gpt, previously integrated into the human chromosome. Clones of SV/HF cells bearing chromosome 6 displayed limited potential for cell division and morphological characteristics of senescent cells. The loss of chromosome 6 from the suppressed clones correlated with the reappearance of immortal clones. Introduced chromosome 6 in the senescing cells was distinguished from those of parental cells by the analysis for DNA sequences specific for the donor chromosome. Our results further show that suppression of immortal phenotype in SV/HF is specific to chromosome 6. Introduction of individual human chromosomes 2, 8, or 19 did not impart cellular senescence in SV/HF. In addition, introduction of chromosome 6 into human glioblastoma cells did not lead to senescence. Based upon these results we propose that at least one of the genes (SEN6) for cellular senescence in human fibroblasts is present on the long arm of chromosome 6.

Journal ArticleDOI
01 May 1994-Blood
TL;DR: Trisomy 5, structural abnormalities involving the pericentromeric regions of chromosomes 5 and 2, and 1q42 abnormalities were findings distinguishing the karyotypes in hairy cell leukemia from those of other hematologic malignancies.

Journal ArticleDOI
01 Feb 1994-Blood
TL;DR: It is speculated that the other MLL-related infant leukemias may also develop in utero, and that the rearrangements may occur consistently in stem cells or early precursor cells, accounting for the frequency of mixed-lineage leukemia in infants.

Journal ArticleDOI
TL;DR: The results support the suggestion that 47,XXY cells are able to go through meiosis and to form spermatozoa and that a preferential pairing of homologous sex chromosomes in 47, XXY spermatocytes is possible.
Abstract: Human sperm chromosomes from a 46,XY/ 47,XXY male were obtained using the technique of in vitro penetration of zona-free hamster eggs. The analysis of 543 sperm complements shows a significantly increased incidence (0.9%) of hyperhaploid gonosomal 24,XY sets, with a lack of the expected corresponding gonosomal hypohaploidies, and a normal rate of autosomal non-disjunctions. These results support the suggestion that 47,XXY cells are able to go through meiosis and to form spermatozoa. Only 24,XY sperm chromosomal constitutions were observed suggesting a preferential pairing of homologous sex chromosomes in 47,XXY spermatocytes.

Journal ArticleDOI
01 Oct 1994-Genome
TL;DR: Nucleolar organizer regions in Acipenser ruthenus and A. baeri are localized on the telomeric regions of two morphologically different pairs of chromosomes, which suggests that species with 120 chromosomes should be considered diploids and species with 240-250 chromosomesShould be considered tetraploid.
Abstract: Nucleolar organizer regions in Acipenser ruthenus (2n = 118 ± 4) are localized on the telomeric regions of two morphologically different pairs of chromosomes. In A. baeri (2n = 250 ± 8), A. transmontanus (2n = 248 ± 8), and A. naccarii (2n = 246 ± 8) they are localized on eight chromosomes arranged in two quadruplets. Contrary to what is commonly accepted, such distribution suggests that species with 120 chromosomes should be considered diploids and species with 240–250 chromosomes should be considered tetraploid.Key words: Acipenseridae, karyotype, nucleolus organizers, polyploidy.

Journal ArticleDOI
TL;DR: The results confirmed the potential of plant flow cytogenetics and form a solid basis for further progress in this area, and analyzed major problems, and assessed future directions.
Abstract: During the past decade, significant progress has been made in the development of methods for the preparation of plant chromosome suspensions suitable for flow cytometric analysis. In addition to successful classification of chromosomes (flow karyotyping), sorting of single chromosome types with a high degree of purity was reported in several plant species. Sorted chromosomes were used for the establishment of chromosome-specific DNA libraries and for gene mapping. The results confirmed the potential of plant flow cytogenetics and form a solid basis for further progress in this area. This article reviews its current status, analyzes major problems, and assesses future directions.

Journal ArticleDOI
TL;DR: In the course of cytogenetic studies, the detection of a supernumerary additional small marker chromosome is not an uncommon occurrence but in prenatal samples such as CVS or amniocytes there are often difficulties in interpretation.
Abstract: In the course of cytogenetic studies, the detection of a supernumerary additional small marker chromosome is not an uncommon occurrence. In lymphocytes the presence of such a marker, once identified, may be directly correlated with the clinical phenotype but in prenatal samples such as CVS or amniocytes there are often difficulties in interpretation. These difficulties not only involve the identification of the chromatin fragment from which the additional material has been derived but also the prediction of its likely effect upon the phenotype. The first problem is gradually being overcome with the advent of fluorescence in situ hybridisation (FISH) which has the ability to identify chromatin material selectively by using chromosome specific libraries. The difficulty in relating marker to phenotype will only become resolvable by defining not only the original location of the extra material but also how much excess euchromatin is actually present. One of the most common chromosome markers is the inv dup(15) or idic(15), which may represent as many as 50% of the small supernumerary chromosomes detected during routine karyotyping. Buckton et all in their study of 44 marker chromosomes found an inv dup(15) to account for 17 of those detected. In a survey of 16 395 newborn babies they found an incidence of supernumerary markers of 0-24 per 1000. Among 1142 persons with congenital abnormalities, however, the incidence was 10 times higher at 2-63 per 1000. In another study of 5049 newborn babies, 0-06% were found to carry markers, of which 33/64 were inv dup(15).2 The phenotype of probands who carry such a marker varies considerably from apparently unaffected persons to those who are severely mentally retarded. Correlations have been attempted between the severity of the phenotype and the size of the additional marker chromosome but the degree of polymorphism associated with proximal chromosome 15 makes accurate estimation of the amount of

Journal Article
TL;DR: Phenotypically, the proband resembled three previously reported cases of maternal isodisomy for chromosome 7, suggesting that lack of paternal genes from 7q may result in a phenotype of short stature and growth retardation.
Abstract: Uniparental isodisomy resulting from the simultaneous presence of isochromosomes of the p and q arms of a chromosome and absence of a normal homologue is an exceptionally rare event. We have observed a growth-retarded female infant in whom the normal chromosome 7 homologues were replaced by what appeared cytogenetically to be isochromosomes of 7p and 7q. Polymorphic microsatellite loci spanning the length of 7p and 7q were analyzed in the proband and her parents to ascertain the parental origin and extent of heterozygosity of the proband's rearranged chromosomes. These studies demonstrated that the 7p alleles of the proband were derived only from the father, the 7q alleles were derived only from the mother, and there was homozygosity for all chromosome 7 loci analyzed. The mechanisms leading to the formation of the proband's isochromosomes could reflect abnormalities of cell division occurring at meiosis, postfertilization mitosis, or both. We believe that the present case may result from incomplete mitotic interchange in the pericentromeric regions of chromosome 7 homologues, with resolution by sister-chromatid reunion in an early, if not first, zygotic division. Phenotypically, our proband resembled three previously reported cases of maternal isodisomy for chromosome 7, suggesting that lack of paternal genes from 7q may result in a phenotype of short stature and growth retardation.

Journal Article
TL;DR: Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45,X/46,X,r(X) karyotype, and studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed.
Abstract: Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45,X/46,X,r(X) karyotype. Studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed. As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia, nonexpression of the locus even when it is present suggests that these chromosomes are transcriptionally active. We examined the transcriptional activity of ring X chromosomes lacking XIST expression (XISTE-), from three females with severe phenotypes. The two tiny ring X chromosomes studied with an antibody specific for the acetylated isoforms of histone H4 marking transcribed chromatin domains were labeled at a level consistent with their being active. We also examined tow of the XISTE- ring chromosomes to determine whether genes that are normally silent on an inactive X are expressed from these chromosomes. Analyses of hybrid cells show that TIMP, ZXDA, and ZXDB loci on the proximal short arm, and AR and PHKA1 loci on the long arm, are well expressed from the tiny ring X chromosome lacking XIST DNA. Studies of the ring chromosome that has XIST DNA but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: Data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implications.
Abstract: A detailed cytogenetic analysis of 63 non-small cell lung carcinomas (NSCLCs) was carried out for identification of recurrent chromosomal alterations. Most specimens displayed very complex karyotypes with multiple numerical and structural changes (median number, 31). Losses of chromosomes 9 (65% of cases) and 13 (71%) were the most frequent numerical changes. Loss of the Y was often observed in tumors from males. Gain of chromosome 7 was also frequent (41%). Chromosome arms 1p, 1q, 3p, 3q, 6q, 7q, 8q, 9p, 11q, 17p, and 19q were particularly prone to rearrangement. The chromosome arm most often contributing to losses was 9p (79%). Other arms that were frequently lost included 3p, 6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, 22q, and the short arm of each acrocentric chromosome. The percentage of cases with loss of 3p was significantly higher in squamous cell carcinomas (94%) than in adenocarcinomas (60%). There was also a statistically significant increase in the proportion of cases with gains of 1q, 7p, and 11q in adenocarcinomas compared to squamous cell carcinomas. Several recurrent isochromosomes and unbalanced exchanges were found. Among these was i(5p), which was observed in nine tumors, eight of which displayed adenomatous features. An i(8q) was identified in six cases, including five adenocarcinomas. Double minutes and/or homogeneously staining regions were seen in seven specimens. These data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implications.

Journal ArticleDOI
TL;DR: It is confirmed that a subset of colorectal adenomas exists that have only numerical chromosome aberrations, and this finding supports the previous conclusion that loss of material from distal l p is an early event in coloreCTal tumorigenesis, but that other cytogenetic aberration follow and typically are present already at the adenomatous stage.
Abstract: Cytogenetic analysis of short-term cultures from colorectal adenomas revealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7 was found as the sole change in one of the tumors and together with other numerical changes in another. A + 7 was also present in one case with structural aberrations. Other recurrent numerical aberrations were −14 and −18, both found in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14 was lost in one of the tumors with only numerical changes. The chromosome most often involved in structural aberrations was chromosome I. In 6 cases, the rearrangements led to changes in l p, always with loss of material. The breakpoints were at l p32–36. One adenoma had deletion of l p as the only change. Other chromosomes that were involved in changes in more than 2 cases were chromosomes 8, 13, and 17. These rearrangements typically led to gain of 8q and 13q and loss of 17p. The adenomas with structural abnormalities were generally larger and had a higher degree of dysplasia than did the adenomas with numerical changes only or those with a normal karyotype. All adenomas with a tubulovillous or villous architecture had structural rearrangements. Our findings confirm that a subset of colorectal adenomas exists that have only numerical chromosome aberrations. They also support our previous conclusion that loss of material from distal l p is an early event in colorectal tumorigenesis, but that other cytogenetic aberrations follow and typically are present already at the adenomatous stage. The accumulation of chromosome-level mutational events in adenomas correlates with the pathologic features: the more malignancy-like the phenotype, the more complex the karyotype. There seems to be no single aberration that distinguishes colorectal adenomas from carcinomas, however. Genes Chromosom Cancer 10:190–196 (1994). © 1994 Wiley-Liss, Inc.

Journal ArticleDOI
15 May 1994-Blood
TL;DR: The results show that APL patients with cytogenetically normal chromosomes 15 and 17 may, nevertheless, have involvement of both PML and RARA genes defining a subgroup of APL, t(15;17)-negative/PML-RARA-positive which is analogous to Philadelphia chromosome-negative/BCR-ABL-positive CML.

Book ChapterDOI
01 Jan 1994
TL;DR: These studies have shown that heterochromatin patterns observed in pachytene chromosomes of maize can be detected in mitotic chromosomes by C-banding and has proved useful for chromosome characterization and identification.
Abstract: Cytogenetic studies of both plants and animals have been considerably enhanced by differential staining techniques developed since the pioneering studies of Casperson et al. with fluorescent stains (1968, 1969a,b). The first non-fluorescent banding technique (employing the Giemsa stain) was developed by Pardue and Gall (1970). The Giemsa stain has an obvious advantage over fluorescent stains in that the researcher can utilize ordinary light microscopy and permanent preparations. Many researchers have applied chromosome banding techniques in research on maize and its wild relatives (Horn and Waiden 1971; Vosa and Marchi 1972; Hadlaczky and Kaiman 1975; Sachan and Tanaka 1976; Ward 1980; Mastenbroek and de Wet 1983; Aguiar-Perecin and Vosa 1985; Bernard and Jewell 1985; Gu et al. 1985; Laurie and Bennett 1985; Rayburn et al. 1985; Kakeda et al. 1990; Porter and Rayburn 1990). In brief, these studies have shown that heterochromatin patterns observed in pachytene chromosomes of maize can be detected in mitotic chromosomes by C-banding. In other preparations, the knobs on the maize chromosomes are not visible at mitotic metaphase where the chromosomes have been estimated to be approximately 13 × shorter than at meiotic midpachynema (Filion and Waiden 1973). The C-banding technique of mitotic chromosomes apparently detects the heterochromatin present in the knobs visible at pachynema in meiosis; the knobs contain a highly repeated 185-bp DNA sequence (Peacock et al. 1981). The C-banding technique has proved useful for chromosome characterization and identification because the C-banding patterns are heritable and remain discernible throughout the mitotic and meiotic cell cycles.

Journal ArticleDOI
TL;DR: The distribution of the highly conserved eukaryotic telomeric (TTAGGG)n sequence was investigated in chicken metaphase chromosomes using the FISH technique and the significance may lie in pointing to structural events that might have occurred during the process of karyotype evolution.
Abstract: The distribution of the highly conserved eukaryotic telomeric (TTAGGG)n sequence was investigated in chicken metaphase chromosomes using the FISH technique. Besides the expected telomeric locations, interstitial as well as centromeric locations of the (TTAGGG)n repeat were observed on several macrochromosomes. The microchromosomes display three discrete patterns of labeling with this repeat. The significance of this extreme-different distribution of the telomeric related sequence in chicken chromosomes may lie in pointing to structural events that might have occurred during the process of karyotype evolution.