Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “clonal 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 1,045 records · Page 58Linked to original sources
PubMed1995

p53 protein expression and nuclear DNA content in breast intraductal proliferations.

Immunohistochemical analysis of the p53 gene protein and cytometric assessment of nuclear DNA were performed in a series of 51 cases of intraductal breast proliferation. The series included 22 cases of intraductal hyperplasia without atypia, 6 cases of intraductal hyperplasia with atypia, and 23 cases of pure intraductal carcinoma. Expression of p53 protein was detected in one case of intraductal hyperplasia without atypia (4.5 per cent), one case of intraductal hyperplasia with atypia (16.6 per cent) and six cases of intraductal carcinoma (26.0 per cent). No significant correlation was observed between p53 expression and histological subtype of intraductal carcinoma. Aneuploidy was demonstrated in two cases of intraductal hyperplasia with atypia (33.3 per cent) and in 18 cases of intraductal carcinoma (78.2 per cent). All cases of intraductal hyperplasia without atypia were euploid. No significant association was observed between p53 protein expression and ploidy in intraductal hyperplasia. The only case of intraductal hyperplasia without atypia positive for p53 was euploid, whereas the only p53-positive case of intraductal hyperplasia with atypia was aneuploid. Among the intraductal carcinomas, only the aneuploid cases showed positivity for p53, regardless of histological subtype. The results suggest that some of the changes observed in invasive breast carcinoma, such as p53 expression and aneuploidy, are already present in breast intraductal proliferation, especially in areas with atypia and in intraductal carcinoma. The expression of p53 in breast intraductal proliferation may reflect the acquisition of p53 gene mutations in cells unable adequately to repair DNA damage, with genomic instability which would lead to clonal expansion and putative evolution to invasive disease.

Breast↗
PubMed1998

Acute myeloid leukemia after azathioprine treatment for autoimmune diseases: association with -7/7q-.

Azathioprine is used as an immunosuppressant in a variety of clinical situations, and its prolonged use is associated with an increased risk of solid malignancies. Three patients (one with rheumatoid arthritis and two with systemic lupus erythematosus) treated with azathioprine for 3 to 7 years developed acute myeloid leukemia (AML). The total cumulative doses of azathioprine varied from 89-260 g. An antecedent prolonged pancytopenic phase suggestive of myelodysplasia developed in all the cases. Morphological analysis showed AML with trilineage myelodysplastic features in residual marrow cells in all the cases. Karyotypic analysis showed deletion of the long arm of chromosome 7 (7q-) in one case and monosomy 7 (-7) in two cases. These were chromosomal aberrations typically associated with mutagen- or therapy-related AML. Fluorescence in situ hybridization with a chromosome-7-specific DNA probe was used to investigate the distribution of the monosomy 7 clone in two cases. Monosomy 7 was demonstrated in both the leukemic blasts and the residual myeloid cells of various stages of differentiation. This finding indicated that the leukemia had evolved from a mutated clone that was capable of terminal differentiation, which was consistent with the biological characteristics of the myelodysplastic syndromes. These cases represented therapy-related AML, as evidenced by clincopathological features, karyotypic aberrations of 7q-/-7, and demonstration of leukemic evolution from an underlying clonal myeloid disorder. The data support the hypothesis that azathioprine might be directly mutagenic.

Acute Disease↗
PubMed2025

Doblin: inferring dominant clonal lineages from high-resolution DNA barcoding time series.

MOTIVATION: The lineage dynamics and history of cells in a population reflect the interplay of evolutionary forces they experience, including mutation, drift, and selection. When the population is polyclonal, lineage dynamics also manifest the extent of clonal competition among co-existing mutational variants. If the population exists in a community of other species, the lineage dynamics could also reflect the population's ecological interaction with the rest of the community. Recent advances in high-resolution lineage tracking via DNA barcoding, coupled with next-generation sequencing of bacteria, yeast, and mammalian cells, allow for precise quantification of clonal dynamics in these organisms. RESULTS: In this work, we introduce Doblin, an R suite for identifying dominant barcode lineages based on high-resolution lineage tracking data. We first benchmarked Doblin's accuracy using lineage data from evolutionary simulations, showing that it recovers the clones' identity and relative fitness in the simulation. Next, we applied Doblin to analyze clonal dynamics in laboratory evolutions of Escherichia coli populations undergoing antibiotic treatment and in colonization experiments of the gut microbial community. Doblin's versatility allows it to be applied to lineage time-series data across different experimental setups. AVAILABILITY AND IMPLEMENTATION: Doblin is available on CRAN (https://CRAN.R-project.org/package=doblin) and Github (https://github.com/dagagf/doblin).

DNA Barcoding, Taxonomic↗
PubMed2000

Renal cell carcinoma with rhabdoid features.

Neoplasms with rhabdoid features have been reported at many anatomic sites. In the kidney, rhabdoid tumors are typically found in children, whereas only rare examples have been reported in adults. Little is known of renal cell carcinomas (RCCs) that exhibit rhabdoid features. The objective of this study was to determine the incidence of RCC with rhabdoid attributes and characterize the histologic, immunophenotypic, and ultrastructural features by retrospective analysis of 480 consecutively identified cases of RCC in radical nephrectomy specimens. Immunohistochemical evaluation was performed in cases with rhabdoid foci using a panel of antibodies to pancytokeratin (pan-CK), CK7, CK20, epithelial membrane antigen (EMA), S-100 protein, desmin, vimentin, neuron-specific enolase (NSE), muscle-specific actin (MSA), smooth muscle actin (SMA), human melanoma, black-45 (HMB-45), and glial fibrillary acidic protein (GFAP). Electron microscopy was also performed in selected cases. The presence and extent of rhabdoid foci in relation to pathologic stage and grade were assessed. Twenty-three of 480 cases of RCC (4.7%) exhibited rhabdoid features. The 23 patients were all adults with a mean age of 61.8 years (age range, 33-84 yrs). Fifteen of the patients were men and eight were women. Histologically, the rhabdoid foci were typified by sheets and clusters of variably cohesive, large epithelioid cells with vesicular and often eccentric nuclei, prominent nucleoli, and large, paranuclear intracytoplasmic hyaline globules (inclusions). The presence of these rhabdoid features was related to high histologic Fuhrman grade of the nonrhabdoid carcinoma component, with an incidence of 0 of 84 grade I cases, eight of 300 grade 2 cases (2.6%), six of 70 grade 3 cases (8.9%), and nine of 26 grade 4 cases (34.6%; p = 3 x 10(-9)). The rhabdoid foci were all high grade. The presence of rhabdoid foci was also found in higher stage carcinomas. A total of 52% (12 of 23) of RCC cases with rhabdoid features exhibited extrarenal extension compared with 28% (24 of 92) of contemporary RCCs without rhabdoid features (p = 0.03). The size of the rhabdoid component ranged from 1 mm to more than 2 cm and comprised 1% to 50% of the renal mass. Immunoreactivity for vimentin (100%), NSE (79%), and panCK (56%) was present in the majority of cases. Substantial percentages of cases were immunopositive for EMA (47%) and S-100 protein (37%), with minimal to no immunohistochemical reactivity for CK7 (5%), SMA (5%), CK20 (0%), desmin (0%), MSA (0%), HMB-45 (0%), and GFAP (O%). A distinctive globular, paranuclear reaction pattern was found for the cytokeratin, EMA, and vimentin immunostains. Ultrastructurally, the rhabdoid cells had paranuclear intermediate filament aggregates or paranuclear condensation of organelles, often associated with peripheral vacuolization. Adult RCCs may harbor a rhabdoid component, and these neoplasms can be regarded as "composite" tumors. Rhabdoid elements are important to identify because of their high-grade nature, and association with high stage. Adult RCC with rhabdoid elements should be distinguished from pure rhabdoid tumors of kidney, in light of their clinicopathologic differences. Rhabdoid differentiation in adult renal cell carcinoma may represent clonal divergence and/ or evolution, and emergence of a particularly aggressive element.

Adult↗
PubMed2006

Identification of intergenomic recombinations in unisexual salamanders of the genus Ambystoma by genomic in situ hybridization (GISH).

Unisexual salamanders in the genus Ambystoma (Amphibia, Caudata) are endemic to eastern North America and are mostly all-female polyploids. Two to four of the bisexual species, A. laterale, A. jeffersonianum, A. texanum and A. tigrinum, contribute to the nuclear genome of unisexuals and more than 20 combinations that range from diploid to pentaploid have been identified in this complex. Because the karyotypes of the four bisexual species are similar, homologous and homoeologous chromosomes in the unisexuals can not be distinguished by conventional or banded karyotypes. We chose two widespread unisexual genomic combinations (A.laterale-2 jeffersonianum [or LJJ] and A. 2 laterale-jeffersonianum [or LLJ]) and employed genomic in situ hybridization (GISH) to identify the genomes in these unisexuals. Under optimum conditions, GISH reliably distinguishes the respective chromosomes attributed to both A.laterale and A. jeffersonianum. Of four populations examined, two were found to have independently evolved homoeologous recombinants that persist in both LJJ and LLJ individuals. Our results refute the previous hypothesis of clonal integrity and independent evolution of the genome combinations in these unisexuals. Our data provide evidence for intergenomic interactions between maternal chromosomes during meiosis in unisexuals and help to explain previously observed non-homologous bivalents and/or quadrivalents among lampbrush chromosomes that were possibly initiated by partial homosequential pairing among the homo(eo)logues. To explore the utility of GISH in other members of the complex, probes developed from A. laterale were also applied to unisexuals that contained A. tigrinum and A. texanum genomes. GISH is an effective tool that can be used to identify and to quantify genomic constituents and to investigate intergenomic interactions in unisexual salamanders. GISH also has potential application to examine possible genomic evolution in other unisexuals.

Ambystoma↗
PubMed2000

The TEL-AML1 fusion accompanied by loss of the untranslocated TEL allele in B-precursor acute lymphoblastic leukaemia of childhood.

The TEL-AML1 fusion which results from the t(12;21) rearrangement in childhood B-precursor acute lymphoblastic leukaemia (B-precursor ALL) is often accompanied by loss of the untranslocated TEL allele. From 32/109 children with B-precursor ALL screened for these abnormalities, we found evidence for del 12p, including the loss of the untranslocated TEL allele, to be the secondary event to take place in the leukaemic cells from those patients positive for these abnormalities. This suggests that the initial or predisposing event is the generation of a TEL-AML1 fusion, followed by the promoting event of a deletion of a gene(s) on 12p. A striking characteristic of the leukaemic cells in 61% of the patients showing t(12:21). was the substantial evolution of the primary clonal line containing the reciprocal TEL-AML1 fusion. We were able to show loss of normal TEL in the same patients by interphase fluorescence in situ hybridisation (FISH) analysis and reverse-transcriptase polymerase chain reaction (RT-PCR).

Alleles↗
PubMed1999

Karyotype evolution in a case of uterine angioleiomyoma.

Clonal karyotypic alterations of a uterine angioleiomyoma of a 41-year-old woman are reported. Cytogenetically a stemline of the tumor and two related subclones with additional abnormalities due to karyotypic evolution were identified: 46,X,t(X;11)(p11.4;p15)/46, idem,inv(2)(p15q13)/46, idem,inv(2)(p15q13),t(5;20)(q13;q13.2). None of the aberrations observed in the present case has been reported in uterine smooth muscle tumors before.

Adult↗
PubMed2002

Viral evolution during structured treatment interruptions in chronically human immunodeficiency virus-infected individuals.

We analyzed the evolution of the human immunodeficiency virus type 1 (HIV-1) env gene in 12 chronically infected individuals who underwent structured treatment interruptions (STIs). Analyses of length variation and of clonal sequences demonstrated highly unpredictable evolution, which may limit the strengthening of HIV-specific immune responses by STIs because of the variability in exposure to viral antigens.

Adult↗
PubMed1996

Evolution of fitness in experimental populations of vesicular stomatitis virus.

The evolution of fitness in experimental clonal populations of vesicular stomatitis virus (VSV) has been compared under different genetic (fitness of initial clone) and demographic (population dynamics) regimes. In spite of the high genetic heterogeneity among replicates within experiments, there is a clear effect of population dynamics on the evolution of fitness. Those populations that went through strong periodic bottlenecks showed a decreased fitness in competition experiments with wild type. Conversely, mutant populations that were transferred under the dynamics of continuous population expansions increased their fitness when compared with the same wild type. The magnitude of the observed effect depended on the fitness of the original viral clone. Thus, high fitness clones showed a larger reduction in fitness than low fitness clones under dynamics with included periodic bottleneck. In contrast, the gain in fitness was larger the lower the initial fitness of the viral clone. The quantitative genetic analysis of the trait "fitness" in the resulting populations shows that genetic variation for the trait is positively correlated with the magnitude of the change in the same trait. The results are interpreted in terms of the operation of Muller's ratchet and genetic drift as opposed to the appearance of beneficial mutations.

Adaptation, Physiological↗
PubMed2001

The value of clonality in the diagnosis and follow-up of patients with cutaneous T-cell infiltrates.

The diagnosis of early stages of cutaneous T-cell lymphoma (CTCL) is often difficult, especially for lesions that are at the borderline between reactive and neoplastic skin T-cell infiltrates. T-cell monoclonality in these lesions is considered by some to be an important prognostic factor of neoplastic evolution, whereas others claim that clonality can also be found in benign skin infiltrates and is therefore of limited diagnostic value. To address this controversy, the authors analyzed retrospectively eight patients with lymphocytic skin lesions who progressed to CTCL, and three patients with recurrent T-cell lymphocytic infiltrates who had not developed CTCL. From a total of 65 biopsies of eight progressing patients, 32 were diagnosed as histologically malignant and 33 were diagnosed as benign or borderline. The authors found clonality by either polymerase chain reaction or Southern blot analysis in 88% of malignant and in 79% of nonmalignant lesions. None of the 37 biopsies of non-progressing patients was clonal. These results indicate strongly that the presence of monoclonality in T-cell skin infiltrates is related closely to the risk of developing CTCL. The value of clonality as a marker of malignancy is supported by the absence of T-cell clonal populations in all infiltrates from patients who had not progressed to lymphoma.

Blotting, Southern↗
PubMed2006

Clonal adaptive radiation in a constant environment.

The evolution of new combinations of bacterial properties contributes to biodiversity and the emergence of new diseases. We investigated the capacity for bacterial divergence with a chemostat culture of Escherichia coli. A clonal population radiated into more than five phenotypic clusters within 26 days, with multiple variations in global regulation, metabolic strategies, surface properties, and nutrient permeability pathways. Most isolates belonged to a single ecotype, and neither periodic selection events nor ecological competition for a single niche prevented an adaptive radiation with a single resource. The multidirectional exploration of fitness space is an underestimated ingredient to bacterial success even in unstructured environments.

Adaptation, Physiological↗
PubMed2001

Genetic conflict and conditional altruism in social aphid colonies.

Although kin selection is central to the modern study of social evolution, recent studies of social species have revealed that no simple relationship exists between levels of kinship and sociality. The soldier-producing aphids are unique among highly social animals because, barring movement by aphids between colonies, they occur in clonal groups of genetically identical individuals. Potentially, clonality simplifies efforts to understand social evolution in aphids by obviating issues of intragroup conflict. However, we report here high levels of clonal mixing and conflict in an aphid society. The gall-dwelling colonies of a social aphid species (Pemphigus obesinymphae) are not pure clones, but are invaded by large numbers of aphids from other clones. Intruders behave and develop selfishly once they have invaded a colony of nonkin. They refrain from risky defensive behaviors and accelerate their own development into reproductive rather than defensive stages. This conditionality in the social life of P. obesinymphae reveals complex dynamics and a degree of behavioral plasticity not previously known in aphid societies.

Animals↗
PubMed2000

Analysis of European mtDNAs for recombination.

The standard paradigm postulates that the human mitochondrial genome (mtDNA) is strictly maternally inherited and that, consequently, mtDNA lineages are clonal. As a result of mtDNA clonality, phylogenetic and population genetic analyses should therefore be free of the complexities imposed by biparental recombination. The use of mtDNA in analyses of human molecular evolution is contingent, in fact, on clonality, which is also a condition that is critical both for forensic studies and for understanding the transmission of pathogenic mtDNA mutations within families. This paradigm, however, has been challenged recently by Eyre-Walker and colleagues. Using two different tests, they have concluded that recombination has contributed to the distribution of mtDNA polymorphisms within the human population. We have assembled a database that comprises the complete sequences of 64 European and 2 African mtDNAs. When this set of sequences was analyzed using any of three measures of linkage disequilibrium, one of the tests of Eyre-Walker and colleagues, there was no evidence for mtDNA recombination. When their test for excess homoplasies was applied to our set of sequences, only a slight excess of homoplasies was observed. We discuss possible reasons that our results differ from those of Eyre-Walker and colleagues. When we take the various results together, our conclusion is that mtDNA recombination has not been sufficiently frequent during human evolution to overturn the standard paradigm.

Africa↗
PubMedDate not supplied

T cell receptor clonal diversity following allogeneic marrow grafting.

The advent of methods for exploring T cell clonal diversity in detail by using the reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify the CDR3 segment of the T cell receptor (TCR) Vbeta gene represents a powerful tool for analyzing and monitoring T cell clones that may be responsible for graft-versus-host disease (GVHD) or specific immunity. In this report we describe studies of the posttransplant peripheral blood T cell repertoire in two patients receiving marrow grafts from unrelated donors. One patient received an unmodified T cell replete graft and the second patient received a T cell-depleted marrow graft. Both patients were matched with their donors for HLA-A and -B, but differed for a DRB1 minor mismatch. The patient receiving a TCD graft showed a progressive loss of expression of several Vbeta genes during the first 6 months, although expression of some Vbeta genes appeared transiently following reduction of immune suppression therapy and evidence of acute GVHD. Spectratyping of CDR3 segments revealed evolution of new clones and clonal deletion during the posttransplant period. This method in conjunction with a functional analysis and monitoring of host-reactive clones would provide a new approach for evaluating the activity of immunosuppressive therapy.

Adult↗
PubMed1997

Role of mutator alleles in adaptive evolution.

Because most newly arising mutations are neutral or deleterious, it has been argued that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. But up to one per cent of natural bacterial isolates are 'mutator' clones that have high mutation rates. We consider here whether high mutation rates might play an important role in adaptive evolution. Models of large, asexual, clonal populations adapting to a new environment show that strong mutator genes (such as those that increase mutation rates by 1,000-fold) can accelerate adaptation, even if the mutator gene remains at a very low frequency (for example, 10[-5]). Less potent mutators (10 to 100-fold increase) can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments.

Adaptation, Physiological↗
PubMed2003

Follow-up of the T-cell clonality in Sezary patients treated by extracorporeal photopheresis using a new assay: the immunoscope technique.

Sezary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma related to the malignant proliferation of clonal CD4+ T-cells. Extracorporeal photochemotherapy (ECP) may induce a transient improvement of the clinical signs but it's efficiency is discussed. In order to investigate the T-cell clonality in the peripheral blood of patients with Sezary syndrome and to monitor its evolution in 8 patients treated by ECP, we used the Immunoscope technique. In one patient, we observed a decrease of the T-cell clonality from 15.6% to 0%, paralleling a complete remission of the clinical disease with a disappearance of the circulating Sezary cells. In the other cases, the evolution of the relative frequency paralleled the clinical status of the patient. In 3 cases, we observed a quick-acting direct cytotoxicity of the association 8MOP + UVA on the T-cell clone present in the cellular product. Immunoscope technique appears to be an efficient assay to appreciate the amount of tumoral cells and monitor the evolution of the clonal component in Sezary syndrome.

Aged↗
PubMed2003

Protein evolution and codon usage bias on the neo-sex chromosomes of Drosophila miranda.

The neo-sex chromosomes of Drosophila miranda constitute an ideal system to study the effects of recombination on patterns of genome evolution. Due to a fusion of an autosome with the Y chromosome, one homolog is transmitted clonally. Here, I compare patterns of molecular evolution of 18 protein-coding genes located on the recombining neo-X and their homologs on the nonrecombining neo-Y chromosome. The rate of protein evolution has significantly increased on the neo-Y lineage since its formation. Amino acid substitutions are accumulating uniformly among neo-Y-linked genes, as expected if all loci on the neo-Y chromosome suffer from a reduced effectiveness of natural selection. In contrast, there is significant heterogeneity in the rate of protein evolution among neo-X-linked genes, with most loci being under strong purifying selection and two genes showing evidence for adaptive evolution. This observation agrees with theory predicting that linkage limits adaptive protein evolution. Both the neo-X and the neo-Y chromosome show an excess of unpreferred codon substitutions over preferred ones and no difference in this pattern was observed between the chromosomes. This suggests that there has been little or no selection maintaining codon bias in the D. miranda lineage. A change in mutational bias toward AT substitutions also contributes to the decline in codon bias. The contrast in patterns of molecular evolution between amino acid mutations and synonymous mutations on the neo-sex-linked genes can be understood in terms of chromosome-specific differences in effective population size and the distribution of selective effects of mutations.

Animals↗
PubMed2000

Adaptive dynamics in diploid, sexual populations and the evolution of reproductive isolation.

Evolutionary branching is the process whereby an initially monomorphic population evolves to a point where it undergoes disruptive selection and splits up into two phenotypically diverging lineages. We studied evolutionary branching in three models that are ecologically identical but that have different genetic systems. The first model is clonal, the second is sexual diploid with additive genetics on a single locus and the third is like the second but with an additional locus for mate choice. Evolutionary branching occurred under exactly the same ecological circumstances in all three models. After branching the evolutionary dynamics may be qualitatively different. In particular, in the diploid, sexual models there can be multiple evolutionary outcomes whereas in the corresponding clonal model there is only one. We showed that evolutionary branching favours the evolution of (partial) assortative mating and that this in turn effectively restores the results from the clonal model by rendering the alternative outcomes unreachable except for the one that also occurs in the clonal model. The evolution of assortative mating during evolutionary branching can be interpreted as the initial phase of sympatric speciation with phenotypic divergence and partial reproductive isolation.

Adaptation, Physiological↗