Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “karyotype evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed2002

Clinical course of thrombocytopenia in patients treated with imatinib mesylate for accelerated phase chronic myelogenous leukemia.

We studied 28 patients with accelerated phase chronic myelogenous leukemia (CML) who were enrolled on the Novartis expanded access study 114. Diagnosis of accelerated phase CML was based on karyotypic evolution (n = 9) and hematologic criteria (n = 18). All patients were begun on 600 mg/day of imatinib mesylate. Dose reductions to 400 mg/day and then 300 mg/day were prescribed for an absolute neutrophil count (ANC) of <0.5/microl or a platelet count of <20,000/microl. Twenty-seven of the 28 patients continued treatment for a median of 34 weeks. Eleven patients developed thrombocytopenia following an average of 8.4 +/- 1.4 weeks of therapy. The onset of thrombocytopenia was associated with disease progression in one patient and a decline in bone marrow megakaryocytes in the other 10. Nine patients recovered to a platelet count of >20,000/microl after an average of 19.7 +/- 1.8 weeks. Patients who developed thrombocytopenia had a longer duration of disease (9.39 vs. 4.35 years; P < 0.01) and were more likely to be diagnosed with accelerated phase CML by hematologic criteria. Hematologic responses in patients with and without thrombocytopenia were comparable; however, 31.3% of patients without thrombocytopenia had a complete cytogenetic response compared to none of those with thrombocytopenia. Grade III-IV thrombocytopenia is common in accelerated phase CML and may be a marker for the inability to achieve cytogenetic response using single agent imatinib mesylate.

Antineoplastic Agents↗
PubMedDate not supplied

SV40-transformed fragile (X) amniocytes.

We report SV-40 transformation of female and male fragile X [fra(X)] amniocytes. In the transformants, fra(X) (q27.3) was detected in the 7th passage (9 cell generations) in fra(X) female amniocytes. It was conserved until at least the 20th passage (42 cell generations) although the frequency was reduced or became difficult to detect due to karyotypic evolution in the later generations. Similarly, for the male fra(X) amniocyte line, fra(X) was demonstrated at the 2nd passage (3 cell generations) and persisted until at least the 13th passage (29 cell generations). The prolonged period of reproductive potential of these transformed lines ranging from at least 29-42 generations suggests that the cryopreservation of significant quantities of early passage fra(X) transformed amniocytes will assure a reliable and continuous supply of positive control cells. These lines may be used for fra(X) prenatal diagnostic studies thereby improving the ability to quality control the particular fra(X) induction system being used.

Amniotic Fluid↗
PubMed2006

Sudden blast crisis in patients with Philadelphia chromosome-positive chronic myeloid leukemia who achieved complete cytogenetic remission after imatinib therapy.

BACKGROUND: Most patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) in chronic phase (CP) who receive treatment with imatinib achieve complete cytogenetic remission (CCR), which is correlated tightly with long-term progression-free survival. In these patients, the occurrence of blastic crisis (BC) is rare, and its clinical biologic characteristics are not well known. METHODS: Among 164 patients who received imatinib and were followed for a median of 35 months, 11 patients (6.7%) developed a BC; this was sudden (i.e., it occurred within 3 months of a documented CCR) in 6 patients (54.5%). Those patients were analyzed with respect to their clinical and biologic features and were compared with previous reports. RESULTS: At the time of diagnosis, there were 3 low-risk patients and 3 intermediate-risk patients; 4 patients had received pretreatment with interferon, and 2 patients received only imatinib. The median CP was 18 months, and the median duration of imatinib therapy was 7 months. The median time to CCR was 3 months, and the median time from CCR to BC was 4 months. BC phenotype was lymphoid in 2 patients, myeloid in 3 patients (including 2 patients who had extramedullary localization), and biclonal in 1 patient. Karyotype evolution was detected in 4 patients, whereas a Ph-positive/Ph-negative mosaicism was evident in all 6 patients. One patient presented an M351T mutation. The overall median survival was 3 months. CONCLUSIONS: Sudden BC generally is an uncommon phenomenon that may be relatively frequent in patients with CML who receive imatinib. Clinical and biologic features also seem to characterize this peculiar type of abrupt disease evolution, which intervenes in patients' response to this drug. Close monitoring of disease markers and full disease eradication are warranted.

Adult↗
PubMed1990

Centromere splitting in bladder cancer.

Cytogenetic studies on a bladder carcinoma, carried out using short time cultures, showed centromere splitting (CS) mainly affecting chromosomes 22, 13, 14, 21, 15, 20, 12, 7, 17, and 18. Clonal trisomies and monosomies were also detected. Our case is the first description of CS in bladder tumor cells. Our results suggest that CS is an early phenomenon in the karyotypic evolution of this case; it can be considered a primary, yet unspecific, chromosome change related to aneuploidy in bladder cancer.

Aneuploidy↗
PubMed1987

The physical map of Mus musculus chromosome 11 reveals evolutionary relationships with different syntenic groups of genes in Homo sapiens.

The physical localization of sequences homologous to three cloned genes was determined by in situ hybridization to metaphase chromosomes. Previous work had assigned the skeletal myosin heavy chain gene cluster (Myh), the functional locus for the cellular tumor antigen p53 (Trp53-1), and the cellular homologue of the viral erb-B oncogene (Erbb) to Mus musculus chromosome 11 (MMU11). Our results provide regional assignments of Myh and Trp53-1 to chromosome bands B2----C, and of Erbb to bands A1----A4. Taken together with in situ mapping of three other loci on MMU 11 (Hox-2 homeobox-containing gene cluster, the Sparc protein, and the Colla-1 collagen gene), which have been reported elsewhere, these data allowed us to construct a physical map of MMU11 and to compare it with the linkage map of this chromosome. The map positions of the homologous genes on human chromosomes suggest evolutionary relationships of distinct regions of MMU11 with six different human chromosome arms: 1p, 5q, 7p, 16p, 17p, and 17q. The delineation of conserved chromosome regions has important implications for the understanding of karyotype evolution in mammalian species and for the development of animal models of human genetic diseases.

Animals↗
PubMed2004

The centromeric regions of potato chromosomes contain megabase-sized tandem arrays of telomere-similar sequence.

Telomere-similar sequences have been found in non-telomeric regions in various eukaryotic species. Centromeric regions often harbor such interstitial telomeric repeats (ITRs). We isolated a 2.8 kb ITR, pSbTC1, in a diploid potato species Solanum bulbocastanum. DNA sequences related to the pSbTC1 family are widely distributed in different Solanum species. The pSbTC1-related sequences are organized into tandem arrays and located mainly in the centromeric regions of potato chromosomes. Most notably, the pSbTC1-related sequences have undergone extensive amplification and a single array can span up to multiple megabases. These results suggest that the pSbTC1-related sequences are not simple relics of ancient events in karyotype evolution, such as chromosomal fusions. We also demonstrated that the pSbTC1-related sequences are heavily methylated and are associated with highly condensed centromeric heterochromatin.

Base Sequence↗
PubMed1998

Telomeres and mechanisms of Robertsonian fusion.

The Robertsonian (Rb) fusion, a chromosome rearrangement involving centric fusion of two acro-(telo)centric chromosomes to form a single metacentric, is one of the most frequent events in mammalian karyotype evolution. Since one of the functions of telomeres is to preserve chromosome integrity, a prerequisite for the formation of Rb fusions should be either telomere loss or telomere inactivation. Possible mechanisms underlying the formation of various types of Rb fusion are discussed here. For example, Rb fusion in wild mice involves complete loss of p-arm telomeres by chromosome breakage within minor satellite sequences. By contrast, interstitial telomeric sites are found in the pericentromeric regions of chromosomes originating from a number of vertebrate species, suggesting the occurrence of Rb-like fusion without loss of telomeres, a possibility consistent with some form of telomere inactivation. Finally, a recent study suggests that telomere shortening induced by the deletion of the telomerase RNA gene in the mouse germ-line leads to telomere loss and high frequencies of Rb fusion in mouse somatic cells. Thus, at least three mechanisms in mammalian cells lead to the formation of Rb fusions.

Animals↗
PubMed2006

Identification of large-scale human-specific copy number differences by inter-species array comparative genomic hybridization.

Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee, bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla. The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications (SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity.

Animals↗
PubMedDate not supplied

Cytogenetic characterization of the sole Solea senegalensis (Teleostei: Pleuronectiformes: Soleidae): Ag-NOR, (GATA)n, (TTAGGG)n and ribosomal genes by one-color and two-color FISH.

A cytogenetic analysis of the sole Solea senegalensis was carried out using silver staining for the nucleolus organizer region (Ag-NOR) identification, one-color FISH for chromosomal mapping of 45S and 5S ribosomal DNAs (rDNAs), (GATA)n, and (TTAGGG)n, and two-color FISH for co-localization of both rDNAs. The Ag-NORs and the 45S rDNA were mapped to a medium-sized submetacentric chromosomal pair. Hybridization with the 5S rDNA showed a major signal on the short arm of a medium-sized submetacentric chromosome pair and a minor signal on a centromeric site of a small acrocentric chromosome pair. Differences in the Ag-NOR and 45S and 5S rDNAs FISH signal sizes were observed between homologous chromosomes and among individuals. A two-color FISH co-localized 45S and 5S rDNAs to a medium-sized submetacentric chromosomal pair. The hybridization with the telomeric (TTAGGG)n repeat displayed small signals at all chromosomal telomeres. Finally, the (GATA)n probe produced dispersed and small hybridization signals on all chromosome spreads, showing its ubiquitous existence in the genome. These results were compared with those from other Pleuronectiformes and discussed in terms of karyotype evolution.

Animals↗
PubMed2006

Divergent location of ribosomal genes in chromosomes of fish thorny-headed worms, Pomphorhynchus laevis and Pomphorhynchus tereticollis (Acanthocephala).

We studied distribution of ribosomal DNA (rDNA) sequences along with chromosomal location of the nucleolar organizer regions (NORs) in males of two fish parasites, Pomphorhynchus laevis and Pomphorhynchus tereticollis (Acanthocephala). Fluorescence in situ hybridization with 18S rDNA probe identified two clusters of rDNA in each species, but revealed a remarkable difference in their location on chromosomes. In P. laevis, the rDNA-FISH signals were found in long arms of the first chromosome pair and in short arms of the second pair. Whereas in P. tereticollis, rDNA clusters were located in long arms of both the first and second chromosome pairs. The divergent location of rDNA clusters in the chromosome No. 2 supports current classification of P. tereticollis, previously considered a synonym of P. laevis, as a separate species. A possible scenario of the second chromosome rearrangement during karyotype evolution of the two species involves two successive pericentric inversions. In both species, one or two prominent nucleoli were apparent within interphase nuclei stained with either silver nitrate or a fluorescent dye YOYO-1. However, a single large nucleolus was observed in early stages of mitosis and meiosis I regardless the number of rDNA clusters. Nevertheless, two bivalents with silver-stained NORs in diakinesis and two silver-stained sites in early prophase II nuclei indicated that all NORs are active. This means that each Pomphorhynchus NOR generates a nucleolus, but the resulting nucleoli have a strong tendency to associate in a large body.

Acanthocephala↗
PubMed1989

Different homing pattern of isolated mouse lymphoma cells correlates with a different chromosomal pattern.

After 5-20 weeks of in vitro culture of mouse lymphoma cells, a characteristic and reproducible change in cell morphology, clonogenic ability, and homing pattern after intraperitoneal or intravenous injection was observed. Cytogenetic comparison of the two cell populations present before and after the "switch" revealed that the phenotypic changes cannot be due to in vitro karyotype evolution because their chromosomal pattern differed in such a way that it is impossible that they can evolve from each other. It was concluded that two different cell populations are present in the lymphoma and their growth and behavior are influenced by certain circumstances and/or interactions. Apparently one population predominates in the peripheral blood circulation, whereas the other will predominate after prolonged in vitro culturing.

Animals↗
PubMed1996

Loss of telomeric sequences in a ring derived from chromosome 8 in refractory anemia with excess of blasts in transformation.

Using the fluorescence in situ hybridization technique, we analyzed a ring chromosome that appeared as a karyotype evolution in a patient affected by refractory anemia with excess of blasts in transformation. Metaphases hybridized with a chromosome-8-specific centromeric probe indicated that the ring retained the centromere of chromosome 8. Successively, utilizing a probe specific for all human telomeres, we observed that the ring lost telomeric sequences. This study demonstrated that the formation of a ring chromosome in hematologic disorders can cause loss of genetic material not revealed by banding techniques and therefore providing further proof of the advantages of molecular cytogenetic techniques.

Aged↗
PubMed1990

Localization of the gene for interphotoreceptor retinoid-binding protein to mouse chromosome 14 near Np-1.

Interphotoreceptor retinoid-binding protein (IRBP) is a large glycoprotein known to bind retinoids and found primarily in the interphotoreceptor matrix of the retina between the retinal pigment epithelium and the photoreceptor cells. It is thought to transport retinoids between the retinal pigment epithelium and the photoreceptors, a critical role in the visual process. We have used a 900-bp bovine IRBP cDNA fragment to map the corresponding gene, Rbp-3, to mouse chromosome 14 with somatic cell hybrids and have positioned the gene near Np-1 (nucleoside phosphorylase-1) by analysis of the progeny of an intersubspecific backcross. In the human genome, NP maps to human chromosome 14 and RBP3 to human chromosome 10. Thus, these two genes span the putative site of a chromosomal translocation which contributed to divergent karyotype evolution of man and mouse.

Animals↗
PubMed1999

MYCN gene amplification. Identification of cell populations containing double minutes and homogeneously staining regions in neuroblastoma tumors.

Neuroblastoma is the second most common solid tumor occurring in children. Amplification of the MYCN oncogene is associated with poor prognosis. To identify neuroblastoma tumors with MYCN amplification, we studied the number of copies of MYCN in interphase cells by fluorescence in situ hybridization in 20 neuroblastoma patients. MYCN amplification appeared in 7 tumor specimens. Interphase and metaphase studies showed a tumor cell population with both forms of amplification, double minutes and homogeneously staining regions, in two patients. These patients showed a smaller tumor cell subpopulation with the presence of more than one homogeneously staining region, suggesting that gene amplification was undergoing karyotype evolution.

Adolescent↗
PubMed2002

Comparative analysis of two thyroid tumor cell lines by fluorescence in situ hybridization and comparative genomic hybridization.

Tumors and tumor-derived cell lines are typically chromosomally complex and heterogeneous. These features complicate the description of their karyotype. As a first approach to the chromosomal characterization of the two near-triploid thyroid tumor cell lines, BCPAP and FTC133, the techniques of fluorescence in situ hybridization and comparative genomic hybridization were used and compared. Most of the results obtained by the two methods were in good agreement. The follicular-derived cell line FTC133 showed more extensive chromosome variation between cells than the papillary-derived cell line BCPAP. Both cell lines had significant gains in part or whole of chromosomes 1, 11, and 20 and losses in chromosomes 16, 21, and 22. BCPAP cells also had gains in chromosomes 4 and 5 and losses in chromosomes 7, 9, and 10; FTC133 cells had gains in chromosomes 6, 7, 8, 14, 15, and 19. Chromosomes 4 and 5 were the most stable in BCPAP cells; in the FTC133 cells, chromosomes 7 and 19 showed the greatest segregational stability. The results have been discussed in terms of possible karyotype evolution. Moreover, it has been possible to compare the sensitivity limits of the two techniques in the analysis of polyploid tumors.

Chromosome Aberrations↗
PubMed1999

Clinical significance of cytogenetic findings at diagnosis and in remission in childhood and adult acute lymphoblastic leukemia: experience from India.

We report cytogenetic findings in 114 patients of acute lymphoblastic leukemia (ALL), which includes 78 children (< or = 15 years) and 36 adults (16-60 years). Chromosome aberrations were detected in 109 (95%) cases. A lower frequency of hyperdiploidy (15%) in children and a higher frequency of hypodiploidy both in children (38.4%) and adults (44.4%) were found, in contrast to literature. Translocations were detected in one third of adult and pediatric cases. The incidence of t(9;22) was comparatively low in adults (7.7%). Frequency of t(1:19) was also low in overall ALL cases. Various other recurrent abnormalities such as del(6q), abn(11q23), i(9p), abn(12q13), del(7q), and i(17q) were seen in our cases; a striking difference in the incidence of del(6q) (41%) and abn(11q23) (30%) was found in our series versus reported literature. Ploidy distribution indicated association of pseudo- and hypodiploidy with B-lineage, and hypodiploidy with T-lineage in children. The occurrence of del(6q) was more frequent in pediatric ALL with highly aberrant pattern and also with lymphadenopathy. Abn(11q23) was found to be early-B and pre-B specific. Kaplan-Meier analysis of overall survival revealed prognostic value of sex, FAB, immunophenotype, and cytogenetic findings. Females and T-ALL patients had a better prognosis, whereas males and B-ALL patients had poor outcome in overall and pediatric age groups. Prognostic evaluation of cytogenetics indicated translocations as an independent high-risk predictor in childhood (P < 0.008) and adult ALL (P < 0.01). Childhood ALL with t(8;14) and t(4;11) and adults with t(9;22) had poor survival. Cytogenetics of remission marrows demonstrated disappearance of abnormal clones in 31.4%, and expansion in normal clones in 50% of patients. Persistence of original clones and development of new clones were observed in 20% and 33% of patients, respectively; whereas karyotype evolution was identified in 10% of patients. The prognostic significance of cytogenetic findings at diagnosis, and differential cytogenetic response in so-called clinical remission in our study indicated the utmost need for more intensive therapy for eradication of resistant clones, and necessity of sequential cytogenetic follow-up in these patients for identification of minimal residual disease.

Adolescent↗
PubMed1999

Polyploidization and losses of chromosomes 1, 2, 6, 10, 13, and 17 in three cases of chromophobe renal cell carcinomas.

Clonal chromosome aberrations identified after short-term culture are presented for three cases of chromophobe renal cell carcinomas (RCC). All tumors revealed abnormal karyotypes with a varying proportion of polyploid tumor cells. Common numerical abnormalities were combined losses of chromosomes 1, 2, 6, 10, 13, and 17. Clonal karyotypic evolution was demonstrated in one case in which several related clones could be identified. An additional balanced translocation t(3;14)(p24;q22) observed in this case proved to be of constitutional nature by cytogenetic analysis of normal kidney cells and peripheral blood lymphocytes. These cytogenetic findings provide further evidence that chromophobe renal cell carcinomas are characterized by a highly specific combination of chromosomal losses most commonly including chromosomes 1, 2, 6, 10, 13, and 17.

Adenocarcinoma↗
PubMed2002

Genome architecture, rearrangements and genomic disorders.

An increasing number of human diseases are recognized to result from recurrent DNA rearrangements involving unstable genomic regions. These are termed genomic disorders, in which the clinical phenotype is a consequence of abnormal dosage of gene(s) located within the rearranged genomic fragments. Both inter- and intrachromosomal rearrangements are facilitated by the presence of region-specific low-copy repeats (LCRs) and result from nonallelic homologous recombination (NAHR) between paralogous genomic segments. LCRs usually span approximately 10-400 kb of genomic DNA, share >or= 97% sequence identity, and provide the substrates for homologous recombination, thus predisposing the region to rearrangements. Moreover, it has been suggested that higher order genomic architecture involving LCRs plays a significant role in karyotypic evolution accompanying primate speciation.

Behavior↗