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 1,171 records · Page 65Linked to original sources
PubMed2026

Lineage-specific adaptation and resistance in Candida albicans.

Candida albicans exhibits substantial phenotypic and ecological diversity; however, the exact relationship between its population structure, adaptation to specific niches, and antifungal resistance remains incompletely understood. To investigate these evolutionary dynamics, we analyzed the whole-genome sequences from 591 publicly available isolates, integrating nuclear and mitochondrial phylogenomics with ecological and resistance-associated genomic analyses. Phylogenomic analyses resolved 18 core nuclear clusters together with multiple admixed lineages. Strong cytonuclear concordance was noted in the majority of the central lineages, contrasting with a higher discordance among the admixed groups, consistent with recurrent genetic exchange. The analysis revealed that geographic origin explains a larger fraction of genetic variance than anatomical niche, supporting a predominantly generalist population structure. A notable exception was Cluster N16 (Candida africana), which presented a strict genital origin in our dataset (n = 34). Additionally, although the mitochondrial genome exhibits strong purifying selection, candidate residues under diversifying selection correlated with specific niches (e.g., bloodstream) have been identified. Analysis of five resistance-associated genes (ERG11, UPC2, FKS1, TAC1 and FUR1) revealed that resistance-associated variants were generally rare but exhibited distinct gene-specific patterns. In case of ERG11 and FUR1 they were concentrated in a specific clade (N11, N17, and their admixed Group A) and exhibit gene-dependent zygosity patterns. In summary, the evolution of C. albicans appears to be driven by a predominantly clonal model punctuated by episodic genetic exchange, where both ecological adaptation and antifungal resistance mutations exhibit genomic signatures marked by lineage specificity.

Antifungal resistance↗
PubMed2026

Single unscreened carrier triggered ICU outbreak of a KPC-producing Klebsiella pneumoniae which acquired in vivo resistance to ceftazidime-avibactam, and cefiderocol.

BACKGROUND: Carbapenemase-producing Enterobacterales are a major cause of healthcare-associated outbreaks in intensive care units (ICUs), where unrecognized carriers can drive silent transmission. We report an ICU outbreak caused by KPC-producing Klebsiella pneumoniae and the within-host emergence of resistance to ceftazidime-avibactam and cefiderocol in the index case. METHODS: Four ICU patients with five K. pneumoniae isolates identified between July and August 2023 were investigated. Phenotypic, genomic and functional analyses were performed to determine the clonal relatedness of the isolates and elucidate the mechanisms underlying resistance evolution. RESULTS: All isolates belonged to ST512, confirming dissemination of a single high-risk clone. The first isolate recovered from the index patient was susceptible to ceftazidime-avibactam and cefiderocol, but a later isolate obtained during ceftazidime-avibactam therapy acquired resistance to both agents. Genomic analysis revealed a novel KPC variant (KPC-270) carrying a 19-amino-acid duplication. When expressed in Escherichia coli, KPC-270 conferred ceftazidime-avibactam resistance, but it did not fully reproduce the meropenem or cefiderocol phenotype. Efflux inhibition substantially reduced meropenem and cefiderocol MICs in the resistant isolate, and avibactam partially restored cefiderocol activity, supporting multifactorial mechanism. CONCLUSION: This outbreak illustrates how unrecognized multidrug-resistant carriage in the index patient facilitated the nosocomial dissemination of a high-risk ST512 K. pneumoniae clone, followed by rapid resistance evolution during ceftazidime-avibactam therapy. Resistance was multifactorial, involving the novel KPC-270 variant and efflux activity contributing to ceftazidime-avibactam, meropenem and cefiderocol resistance.

Cefiderocol↗
PubMed2006

Genetic mechanisms for loss of encapsulation in polysialyltransferase-gene-positive meningococci isolated from healthy carriers.

Encapsulated Neisseria meningitidis expressing serogroups A, B, C, W-135, or Y remain a major cause of morbidity and mortality globally. This bacterium is, however, a common commensal inhabitant of the human nasopharynx that causes disease infrequently. Isolates obtained from healthy carriers are frequently unencapsulated and therefore essentially avirulent. The lack of capsule can be due to inactivation of capsule synthesis genes by a variety of genetic mechanisms, or the absence of capsule synthesis genes. Analysis of inactivation mechanisms was undertaken in a diverse but representative set of 166 acapsulate meningococci isolated from carriage that possessed capsule synthesis genes. Slipped strand mispairing in the siaA and siaD genes of the capsule synthesis locus was observed in 39 isolates. Insertion sequence (IS) elements (IS1016-like, IS1106 and IS1301) were responsible for the loss of encapsulation in 46 isolates. Irreversible gene silencing events (insertions, deletions, base exchanges) were found in 47 isolates. Two non-synonymous mutations were identified in close vicinity of the putative active site of the UDP-N-acetylglucosamine 2-epimerase encoded by the siaA gene. The mechanisms for loss of encapsulation were not associated with particular meningococcal genotypes. There was no evidence for successive gene silencing events in the capsule genes, suggesting that the irreversible inactivation events observed were the result of short-term, within-host evolution. These observations are consistent with the postulate that particular meningococcal clonal complexes are associated with possession of a capsule and that this association is important for transmission success.

Adolescent↗
PubMed2005

Clinical and microbiological features of Inquilinus sp. isolates from five patients with cystic fibrosis.

Patients with cystic fibrosis (CF) may be colonized with unusual gram-negative bacilli whose identification is difficult and clinical impact unclear. We describe the clinical and microbiological features of five colonizations with organisms belonging to the recently described genus Inquilinus in CF patients. Isolates were identified from Burkholderia cepacia selective medium by means of 16S rRNA analysis. All of them were resistant to colistin, penicillins, cephalosporins, and monobactams but exhibited a remarkable susceptibility to imipenem. One of the five patients was transiently colonized with a nonmucoid isolate, whereas the four other patients were persistently colonized over the period of follow-up (8 to 21 months) with mucoid isolates. Pulsed-field gel electrophoresis of SpeI-digested genomic DNA was powerful for strain genotyping and demonstrated the clonality of Inquilinus sp. colonization for the two patients tested. Clinical evolution after the onset of Inquilinus was heterogeneous, but for at least one patient the lung function worsened and eradication of Inquilinus sp. was unsuccessful despite several imipenem courses. Finally, Inquilinus spp. may represent a new threat for CF patients due to their mucoid characteristic, their multiresistant pattern to antibiotics, and their ability to persist in the respiratory tract.

Alphaproteobacteria↗
PubMed2000

Update of genetics in colorectal carcinomas: genomic instability and somatic evolution.

INTRODUCTION: Currently, there are two contrasting viewpoints on what drives the process of carcinogenesis. The genomic (DNA or chromosomal) instability model contends that an increased mutation rate early in carcinogenesis is necessary for the multistage process, while the somatic evolution model postulates that normal mutation rate with selective advantage and clonal expansion is sufficient to cause cancer. METHODS: Evidence from colorectal carcinoma (CRC) for and against the two models are compared and contrasted. RESULTS: With the exception of hereditary non-polyposis colorectal carcinoma (HNPCC) where DNA instability attributable to mismatch repair deficiency is clearly demonstrated, the majority of CRC appear to progress through the selection of a series of mutations without the need of first acquiring a mutator phenotype. Aneuploidy or chromosomal instability is more likely to be a consequence of non-random selection of mutations in genes residing on the chromosome rather than the direct cause of cancer. Nevertheless, aneuploidy and/or DNA alterations can lead to secondary instability, hence, contributing to the phenotypes associated with carcinoma. CONCLUSIONS: Present knowledge, thus, points to multiple, mutually non-exclusive pathways for different cancer populations, further emphasising tumour heterogeneity.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Cellular and molecular bases of B-cell clonal expansions.

The concept that lymphomagenesis is a multistep process is now widely accepted. Various factors are involved in the development and malignant progression of B-cell lymphoproliferative disorders. The most frequently recognized alterations in these disorders are chromosomal translocations which lead to the activation of proto-oncogenes (c-myc) or genes encoding for proteins involved in the control of the cell cycle (cyclin D1), differentiation (bcl-6) and apoptosis (bcl-2). In addition, genetic changes that inactivate tumor suppressor genes (p53, Rb, p16) have recently been identified. Infectious agents may also play a role in lymphomagenesis either by directly driving B-cell proliferation (EBV) or by inducing a chronic antigenic stimulation (EBV, HCV, HBV, helicobacter pylori). Finally, several data indicate that local cytokine networks and, in particular, autocrine (IL-6, IL-10) and/or paracrine (IL-2, IL-4, IL-6) loops probably play a contributory role in the development and evolution of B-cell lymphoproliferation. In the last few years, the advent of molecular biology techniques has allowed important advances in the definition of the events involved i the earlier phases of lymphoma development. This has been made possible, in particular, by the study of a series of oligoclonal or monoclonal lymphoproliferative disorders characterized by an indolent or "smoldering" clinical course, such as follicular lymphoma and the lymphoproliferation associated with autoimmune diseases, which are at high risk of evolution to a highly malignant lymphoma. In nearly all of these conditions, the clonal B-cells responsible for the early stages of the disease are probably not fully transformed and retain various degrees of responsiveness to a wide variety of microenvironmental stimuli (antigen or autoantigen stimulation, interactions with "reactive" T lymphocytes, local cytokine networks). These latter in turn may induce the regression of pathological lesions, maintain the disease in an active state or contribute to the evolution towards an overtly malignant lymphoma. These findings open new avenues for the design of unconventional strategies of intervention aimed at preventing the malignant evolution of pre-lymphomatous lesions and controlling the clinical course of certain low-grade B-cell lymphomas.

Animals↗
PubMed2006

Immunogenetic factors determining the evolution of T-cell large granular lymphocyte leukaemia and associated cytopenias.

T-cell large granular lymphocyte leukaemia (T-LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T-LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune-mediated bone marrow failure and autoimmune conditions, may promote T-LGL evolution and/or development of cytopenias. The association of T-LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) genotype, KIR/KIR-L mismatch, CTLA-4 (+49 A/G),CD16-158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF-alpha (-308G/A), TGF-beta1 (codons 10 C/T, 25 G/C), IL-10 (-1082 G/A), IL-6 (-174 C/G), and IFN-gamma(+874 T/A). A statistically significant increase in A/A genotype for TNF-alpha-308, IL-10-1082, andCTLA-4 +49 was observed in T-LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR-L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA-A3/11 and HLA-C group 2 (P = 0.03 and 0.01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T-LGL requires future analysis.

Adult↗
PubMed1995

Gene analysis in 18 cases of cutaneous lymphoid infiltrates of uncertain significance.

BACKGROUND AND DESIGN: Patients with cutaneous lymphoid infiltrates that appear reactive histologically and immunophenotypically may develop clinically overt cutaneous lymphoma, suggesting the possibility of misdiagnosis by classical methods. We investigated DNA rearrangement in such cases of lymphoid infiltrates of uncertain significance to determine whether this more sensitive method could detect an occult monoclonal lymphoid proliferation. METHODS AND PATIENTS: Skin biopsy specimens were taken from 18 cutaneous lymphoid infiltrates diagnosed as reactive on the basis of clinical, histopathological, and immunohistochemical criteria. Specimens included 12 cases with mixed lymphoid infiltrates rich in polytypic B cells and inconstant follicle formation and 6 cases with exclusive T-lymphoid infiltrates. Southern blot analysis for immunoglobulin and T-cell-receptor beta-chain gene rearrangements was performed in all cases. RESULTS: No specimen showed T-cell-receptor beta-chain gene rearrangement. Clonal immunoglobulin gene rearrangement was demonstrated in one case with polytypic B cells, but no clinical malignancy has appeared 19 years after disease onset duration and 7 years after detection of the B-cell clone. CONCLUSIONS: In the present series, the results suggest that histological and immunohistological criteria are appropriate to establish the diagnosis of most cases of cutaneous lymphoid infiltrates. The detection of a B-cell clone is remarkable by absence of clinical malignancy, suggesting that such a discovery does not necessarily mean an aggressive evolution. Nevertheless, there is presently no way to predict the prognosis of a clonal lymphoid proliferation, indicating that a long-term follow-up is necessary.

Adult↗
PubMed1976

The myeloproliferative disorders. Correlation between clinical evolution and alterations of granulopoiesis.

Patients with myeloproliferative disorders were prospectively studied by in vitro agar-gel marrow culture technics to evaluate factors involved in the evolution of abnormal granulopoiesis. Marrow granulocytic colony-forming capacity was determined in 78 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia, Di Guglielmo's syndrome, polycythemia vera or essential thrombocythemia. A wide range of marrow colony-forming capacity values was noted early in disease courses; however, in 26 of 33 patients decreased colony-forming capacity was associated with disease transformation into acute myeloid leukemia or other clinically aggressive stages. An increased proportion of abnormally light buoyant density (less than 1.062 g/cm3) colony-forming cells was present in the marrow and peripheral blood of 15 of 16 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia or essential thrombocythemia; in seven of eight patients with greater than 35 per cent abnormally light colony-forming cells their disease subsequently underwent transformation. Elevated levels of urinary colony-stimulating factor output were noted in 17 of 31 patients, and in 10 of 12 patients whose disease subsequently underwent acute transformation within 10 months of study. In six of seven patients who simultaneously had an increased urinary output of colony-stimulating factor and low colony-forming capacity in marrow, transformation occurred within 10 months. These findings indicate that progressive abnormalities of both marrow clonal growth patterns and levels of possible humoral regulatory substances develop during evolution of these diseases. In contrast, patients with idiopathic sideroblastic ineffective erythropoiesis had normal values for marrow colony-forming capacity, proportion of light density colony-forming cells and urinary colony-stimulating factor output, and in none has their disease transformed into acute myeloid leukemia. These in vitro studies appear useful for clinical staging, evaluating prognosis and categorizing patients with myeloproliferative disorders.

Adolescent↗
PubMed2004

Adaptive amplification and point mutation are independent mechanisms: evidence for various stress-inducible mutation mechanisms.

"Adaptive mutation" denotes a collection of processes in which cells respond to growth-limiting environments by producing compensatory mutants that grow well, apparently violating fundamental principles of evolution. In a well-studied model, starvation of stationary-phase lac(-)Escherichia coli cells on lactose medium induces Lac(+)revertants at higher frequencies than predicted by usual mutation models. These revertants carry either a compensatory frameshift mutation or a greater than 20-fold amplification of the leaky lac allele. A crucial distinction between alternative hypotheses for the mechanisms of adaptive mutation hinges on whether these amplification and frameshift mutation events are distinct, or whether amplification is a molecular intermediate, producing an intermediate cell type, in colonies on a pathway to frameshift mutation. The latter model allows the evolutionarily conservative idea of increased mutations (per cell) without increased mutation rate (by virtue of extra gene copies per cell), whereas the former requires an increase in mutation rate, potentially accelerating evolution. To resolve these models, we probed early events leading to rare adaptive mutations and report several results that show that amplification is not the precursor to frameshift mutation but rather is an independent adaptive outcome. (i) Using new high-resolution selection methods and stringent analysis of all cells in very young (micro)colonies (500-10,000 cells), we find that most mutant colonies contain no detectable lac-amplified cells, in contrast with previous reports. (ii) Analysis of nascent colonies, as young as the two-cell stage, revealed mutant Lac(+)cells with no lac-amplified cells present. (iii) Stringent colony-fate experiments show that microcolonies of lac-amplified cells grow to form visible colonies of lac-amplified, not mutant, cells. (iv) Mutant cells do not overgrow lac-amplified cells in microcolonies fast enough to mask the lac-amplified cells. (v)lac-amplified cells are not SOS-induced, as was proposed to explain elevated mutation in a sequential model. (vi) Amplification, and not frameshift mutation, requires DNA polymerase I, demonstrating that mutation is separable from amplification, and also illuminating the amplification mechanism. We conclude that amplification and mutation are independent outcomes of adaptive genetic change. We suggest that the availability of alternative pathways for genetic/evolutionary adaptation and clonal expansion under stress may be exploited during processes ranging from the evolution of drug resistance to cancer progression.

Adaptation, Biological↗
PubMed1992

Karyotype at relapse following allogeneic bone marrow transplantation for chronic myelogenous leukemia.

Eighty-four patients underwent allogeneic or syngeneic bone marrow transplantation as therapy for chronic myelogenous leukemia (CML) during a 5-year period at The Johns Hopkins Oncology Center. We describe the karyotype at relapse in 19 patients who were Ph chromosome positive (Ph+) at diagnosis. Eighty-four percent of patients demonstrated clonal and/or nonclonal chromosome abnormalities in addition to the t(9;22)(q34;q11) at first detection of relapse or later during relapse. These abnormalities included: Ph plus additional clonal abnormalities (three patients), Ph plus nonclonal abnormalities (five patients), Ph plus additional clonal and nonclonal abnormalities (eight patients). Three patients had only the original Ph+ clone. The additional chromosome abnormalities were primarily structural, and entirely different from those most frequently observed during karyotypic evolution in conventionally treated CML. Chromosome 1 was most frequently involved, with 1q32 being the location of three clonal and two nonclonal abnormalities. Other sites included 6p21-22 (the site of two clonal abnormalities), 7p21-22, and 10q21 (the site of two clonal and one nonclonal abnormality each). Chromosomes 5 and 7q, regions of frequent involvement in acute nonlymphocytic leukemia that follows chemotherapy for other malignancies, were infrequently involved. The clinical significance of these additional abnormalities remains undetermined at this time.

Adult↗
PubMed1998

Giardia intestinalis: conservation of the variant-specific surface protein VSP417-1 (TSA417) and identification of a divergent homologue encoded at a duplicated locus in genetic group II isolates.

The stability of the gene encoding TSA417, a 72-kDa variant-specific surface protein (VSP) produced by trophozoites of Giardia intestinalis isolate WB-C6, was investigated in isolates of similar (Assemblage A / Group I) or distinct (Assemblage A / Group II) genotype. Using primers specific for the WB-C6 tsa417 gene, DNA amplified in polymerase chain reactions from genomic DNA indicated the presence, in every isolate, of an intact coding sequence possessing conserved restriction sites diagnostic for this locus (herein designated vsp417-1). Sequence analysis of the DNA amplified from the genomes of genetic Group I ("A-I") isolates revealed complete identity with the published WB-C6 tsa417 (vsp417-1(A-I)) sequence. Equivalent products, amplified from the genomes of genetic Group II ("A-II") isolates, similarly yielded an invariant and apparently allelic 2142-bp coding sequence (designated vsp417-1(A-II)) possessing 79% nucleotide identity with vsp417-1(A-I) and polymorphisms unique to Group II organisms. The encoded polypeptides (VSP417-1(A-I) and VSP417-1(A-II)) are identical at 75% of amino acid positions. Substitutions are concentrated within the N-terminal portions of the proteins, but the overall structure of VSP417-1 has changed little during the evolution of the Group I and Group II genotypes from their common clonal ancestor. An additional 0.7-kb DNA, representing a separate locus (vsp417-5) encoding a 22.3-kDa VSP, was amplified from genetic Group II genomes exclusively but only using particular primer combinations. The vsp417-5(A-II) gene exhibits >85% sequence identity with the 5' and 3' segments of vsp417-1(A-I) and vsp417-1(A-II) but it lacks a 1482-bp segment that comprises the central portion of the vsp417-1 locus. Excision of this segment seems to have occurred by intragenic recombination, possibly initiated by a stem loop formed between palindromic sequences which border the 1482-bp segment within vsp417-1 but which are contiguous in vsp417-5(A-II). The detection by Southern hybridization of additional genomic sequences that share homology with these genes reveals the existence in these two genotypes of a distinctive "vsp417" gene subset.

Amino Acid Sequence↗
PubMed2000

Molecular evolution of multiple recurrent cancers of the bladder.

We describe the reconstruction of bladder tumor development in individual patients spanning periods of up to 17 years. Genomic alterations detected in the tumors were used for hierarchical cluster analysis of tumor subclones. The cluster analysis highlights the clonal relationship between tumors from each patient. Based on the cluster data we were able to reconstruct the evolution of tumors in a genetic tree, where tumors with few aberrations precede those with many genetic insults. The sequential order of the tumors in these pedigrees differs from the chronological order in which the tumors appear. Thus, a tumor with few alterations can be occult for years following removal of a more deranged derivative. Extensive genetic damage is seen to accumulate during the evolution of the tumors. To explain the type and extent of genetic damage in combination with the low stage and grade of these tumors, we hypothesize that in bladder cancer pathogenesis an increased rate of mitotic recombination is acquired early in the tumorigenic process.

Evolution, Molecular↗
PubMed2003

Phylogenetic considerations of clonality, coloniality, and mode of germline development in animals.

The hypothesis that individuality is a derived trait in animals (Buss, '87, The Evolution of Individuality, Princeton, NJ: Princeton University Press; Michod, '99, Darwinian Dynamics, Princeton, NJ: Princeton University Press) can be further tested by a "tree-based" analysis utilizing a comparative methodology and recent phylogenies. We conducted a maximum parsimony analysis in which we mapped character states for clonality, coloniality, and mode of germline development onto four recent phylogenetic hypotheses (Peterson and Eernisse, 2001, Evol Dev 3:170-205). Clonality appears to be a shared primitive character for metazoans. Coloniality, on the other hand, is a derived trait found in relatively few phyla. The germline appears to have been derived at or near the origin of the first bilaterians. The stem-lineage metazoan thus appears to have been a clonal, acolonial organism that exhibited somatic embryogenesis. The stem-lineage bilaterian also was likely clonal and acolonial. Nevertheless, this lineage likely exhibited preformation, i.e., its germline was determined during embryonic development. In addition to supporting the hypothesis that the germline is a derived feature in animals, this analysis is relevant to current debates concerning the nature of the latest common ancestor of the bilaterians.

Animals↗
PubMed1999

The influence of recombination on the population structure and evolution of the human pathogen Neisseria meningitidis.

The extent to which recombination disrupts the bifurcating treelike phylogeny and clonal structure imposed by binary fission on bacterial populations remains contentious. Here, we address this question with a study of nucleotide sequence data from 107 isolates of the human pathogen Neisseria meningitidis. Gene fragments from 12 house-keeping loci distributed around the meningococcal chromosome were analyzed, showing that (1) identical alleles are disseminated among genetically diverse isolates, with no evidence for linkage disequilibrium; (2) different loci give distinct and incongruent phylogenetic trees; and (3) allele sequences are incompatible with a bifurcating treelike phylogeny at all loci. These observations are consistent with the hypothesis that meningococcal populations comprise organisms assembled from a common gene pool, with alleles and allele fragments spreading independently, together with the occasional importation of genetic material from other species. Further, they support the view that recombination is an important genetic mechanism in the generation new meningococcal clones and alleles. Consequently, for anything other than the short-term evolution of this species, a bifurcating treelike phylogeny is not an appropriate model.

Alleles↗
PubMed2002

Clonal mixing in the soldier-producing aphid Pemphigus spyrothecae (Hemiptera: Aphididae).

Illuminating the genetic relationships within soldier-producing aphid colonies is an essential element of any attempt to explain the evolution of the altruistic soldier caste. Pemphigus spyrothecae is a soldier-producing aphid that induces galls on the leaf petioles of its host (trees of the genus Populus). At least a quarter of the aphids within the clonally produced gall population are morphologically and behaviourally distinct first-instar soldiers that defend the gall population from predation. Using field trapping and microsatellites, we investigated the degree of clonal mixing within natural gall populations. Field trapping in the UK showed that all the migrants of P. spyrothecae and of two other Pemphigus species were wingless first-instar soldiers. The average degree of mixing estimated from trapping P. spyrothecae migrants was 0.68% (range = 0-15%). Microsatellite genotyping of 277 aphids from 13 galls collected in Italy revealed an average mixing level of 10.4% (range = 0-59%). Six galls contained more than one clone (range = 2-5 clones). Non-kin aphids were not restricted to the soldier caste but were evenly distributed across instars. An additional gall, from which 527 occupants were genotyped, contained 12 non-kin aphids distributed among nine clones, showing that clonal diversity can be high even when mixing is very low. These observations suggest that although soldiers migrate regularly and can moult and reproduce within foreign galls, clonal mixing in this species is generally low and is unlikely to provide a barrier to the evolution of investment by the aphid clones in an altruistic soldier caste.

Animals↗
PubMed1998

[Treatment of low-grade gastric MALT lymphoma with Helicobacter pylori eradication. Follow-up of the histological and molecular response].

BACKGROUND: Low grade gastric MALT lymphoma is associated to infection with Helicobacter pylori. Also, H. pylori eradication can produce histologic regression of the lymphoma. PATIENTS AND METHODS: This study reports the follow-up of a prospective series of 11 patients with low grade gastric MALT lymphoma, stage I, treated with eradicative therapy for H. pylori. After treatment, patients were followed up with sequential endoscopies to asses the histological and molecular regression of the lymphoma, using a score of the histological lesions and the amplification of the IgH gene with PCR analysis. RESULTS: Helicobacter pylori was eradicated in all patients. In 10(90.9%) histological regression of the lymphoma was demonstrated, in 6 of them in the first control after treatment. In the 10 patients with histological response, PCR analysis demonstrated a polyclonal rearrangement of the IgH gene in 6 (60%) and a clonal band in 4 (40%), that eventually disappeared at 12 (SD 4) months after treatment. In 4 patients with a previous polyclonal rearrangement, a clonal band was occasionally detected in any sequential controls; in 2 of these cases the clonal band disappeared 5 and 7 months after treatment and in the remaining 2 its evolution is not yet known. Nine patients have been followed up and are in remission 18 (SD 8) months after treatment. CONCLUSIONS: Eradication of H. pylori can produce histologic regression in stage I low grade gastric MALT lymphoma, and should be the first therapeutic option. Despite histological regression of the lymphoma, PCR analysis can detect a clonal rearrangement of the IgH gene in 40% of the cases, but its significance remains unknown. Sequential and prolonged follow-up is essential to assess whether this lymphoma can be actually cured with eradication therapy for H. pylori.

Adult↗
PubMed1986

Cytogenetic heterogeneity: its role in tumor evolution.

There is ample evidence that cytogenetic heterogeneity characterizes human solid tumors, despite the opposing influences of clonal origin and selection for tumor-specific chromosome aberrations. Different chromosome patterns are found within individual tumors and among phenotypically similar tumors. Some tumor cell populations contain mixtures of diploid and cytogenetically aberrant cells; others display multiple aberrant clones. The extent and biological significance of chromosomal heterogeneity is contrasted between examples of leukemias and of selected solid tumors (mainly of breast and central nervous system origin). Increasing degrees of chromosomal aberration appear correlated with increasingly malignant biological properties of tumors. Genic and chromosomal instability are potential sources for genetic diversity within all tumors. However, variations in local selective forces and differential survival within an expanding solid lesion may contribute to maintenance of a mixed cell population within the primary tumor. In turn, the resulting heterogeneity may permit selection and increase of aberrant cells that are responsible for tumor progression and metastasis.

Brain Neoplasms↗