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Clonal Origin (clonal + origin)

Distribution by Scientific Domains

Medical Sciences	69%
Life Sciences	23%

Selected Abstracts

Adult extracardiac rhabdomyoma: Light and immunohistochemical studies of two cases in the parapharyngeal space

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2006
Kristine Bjørndal Sørensen MD
Abstract Background. We present two cases of adult rhabdomyoma in the parapharyngeal space. They are rare benign tumors with a characteristic histologic appearance. Methods. The tumors were studied by light and immunohistochemical analysis using stains characteristic of striated muscle fibers. Results. Cross-striation was demonstrated by phosphotungstic acid hematoxylin (PTAH), muscle specific actin, desmin, and myoglobin while dystrophin was expressed in the cell membranes. Clonal origin was confirmed by expression of myosin heavy chain-fast only. Expression of myosin-neonatal and myogenin proved slight proliferation with incipient differentiation in an otherwise mature tumor. Conclusion. The head and neck area harbors 90% of adult rhabdomyomas and should be considered in a differential diagnosis in this region. Immunohistochemistry confirms that the tumors are almost totally mature neoplasms of clonal origin. © 2006 Wiley Periodicals, Inc. Head Neck28: XXX,XXX, 2006 [source]

Clonal origin of multifocal hepatocellular carcinoma

CANCER, Issue 17 2010
Kurt B. Hodges MD
Abstract BACKGROUND: Hepatocellular carcinoma is the most common primary tumor of the liver. Patients frequently have multiple histologically similar, but anatomically separate tumors. The clonal origin of multiple hepatocellular carcinomas is uncertain. METHODS: The authors analyzed 31 tumors from 12 different patients (11 women, 1 man), who had multiple hepatocellular carcinomas involving 1 or both lobes. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue using laser capture microdissection. DNA was analyzed for loss of heterozygosity (LOH), X chromosome inactivation status, and TP53 gene mutations. RESULTS: Ten (83%) of the 12 patients showed LOH in at least 1 of the analyzed microsatellite markers. Concordant LOH patterns between separate hepatocellular carcinomas in individual patients were seen in 8 (80%) of 10 cases, whereas discordant patterns were seen in 2 (20%) of 10 cases. Five (50%) of 10 informative female patients showed identical nonrandom X chromosome inactivation patterns in multiple tumors; 1 case showed discordant nonrandom X chromosome inactivation pattern. TP53 mutations were identified in 8 (67%) of 12 patients. Tumors in 7 (88%) of these 8 patients showed different point mutations. Three patients (Cases 4, 5, and 10) had tumors with additional TP53 point mutations, indicating additional genetic abnormalities in these tumors. CONCLUSIONS: The data suggested that the significant proportion of patients with multifocal hepatocellular carcinomas have tumors of common clonal origin. Cancer 2010. © 2010 American Cancer Society. [source]

PERSPECTIVE: SEX, RECOMBINATION, AND THE EFFICACY OF SELECTION,WAS WEISMANN RIGHT?

EVOLUTION, Issue 2 2000
Austin Burt
Abstract., The idea that sex functions to provide variation for natural selection to act upon was first advocated by August Weismann and it has dominated much discussion on the evolution of sex and recombination since then. The goal of this paper is to further extend this hypothesis and to assess its place in a larger body of theory on the evolution of sex and recombination. A simple generic model is developed to show how fitness variation and covariation interact with selection for recombination and illustrate some important implications of the hypothesis: (1) the advantage of sex and recombination can accrue both to reproductively isolated populations and to modifiers segregating within populations, but the former will be much larger than the latter; (2) forces of degradation that are correlated across loci within an individual can reduce or reverse selection for increased recombination; and (3) crossing-over (which can occur at different places in different meioses) will create more variability than having multiple chromosomes and so will have more influence on the efficacy of selection. Several long-term selection experiments support Weismann's hypothesis, including those showing a greater response to selection in populations with higher rates of recombination and higher rates of recombination evolving as a correlated response to selection for some other character. Weismann's hypothesis is also consistent with the sporadic distribution of obligate asexuality, which indicates that clones have a higher rate of extinction than sexuals. Weismann's hypothesis is then discussed in light of other patterns in the distribution of sexuality versus asexuality. To account for variation in the frequency of obligate asexuality in different taxa, a simple model is developed in which this frequency is a function of three parameters: the rate of clonal origin, the initial fitness of clones when they arise, and the rate at which that fitness declines over time. Variation in all three parameters is likely to be important in explaining the distribution of obligate asexuality. Facultative asexuality also exists, and for this to be stable it seems there must be ecological differences between the sexual and asexual propagules as well as genetic differences. Finally, the timing of sex in cyclical parthenogens is most likely set to minimize the opportunity costs of sex. None of these patterns contradict Weismann's hypothesis, but they do show that many additional principles unrelated to the function of sex are required to fully explain its distribution. Weismann's hypothesis is also consistent with what we know about the mechanics and molecular genetics of recombination, in particular the tendency for chromatids to recombine with a homolog rather than a sister chromatid at meiosis, which is opposite to what they do during mitosis. However, molecular genetic studies have shown that cis -acting sites at which recombination is initiated are lost by gene conversion as a result, a factor that can be expected to affect many fine details in the evolution of recombination. In summary, although Weismann's hypothesis must be considered the leading candidate for the function of sex and recombination, nevertheless, many additional principles are needed to fully account for their evolution. [source]

Sexual or clonal origin?

FEDDES REPERTORIUM, Issue 3-4 2005
A morpho-ecological, molecular analysis in a patch of Ajuga reptans L. (Lamiaceae)
Spatial clonal structure and patch colonisation in Ajuga reptans L. (Lamiaceae), a common stoloniferous semi-rosette plant, were studied using a combined morpho-ecological and molecular genetic approach. Within a natural patch from a forest near Diedorf (Thuringia, Germany), the spatial clonal structure was analysed, correlating both datasets: Morphologically, characteristics of clonal growth and clonal reproduction were studied, the spatial distribution of modules was mapped and merigenet relationships were reconstructed. Samples from the patch and its surroundings, and an additional sample from Berlin were then analysed by AFLP fingerprinting using four different primer combinations to identify genets. Most divergence in banding patterns was already obtained for samples from the Diedorf forest. Within the patch, however, most samples had very similar fingerprints, indicating their belonging to the same genet and hence a clonal origin, although they are morphologically separated into three "plants". Based on AFLP data, the relationships of one sample remained ambiguous; but the correlation with morphological data helped to interpret the pattern and indicated that the sample is probably a dividual of the clone, too. The relevance of the observed vegetative multiplication (clonal growth and subsequent clonal reproduction) for patch colonisation and maintenance are discussed. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) Generativer (sexueller) oder klonaler Ursprung? Eine morpho-ökologische und molekulare Analyse in einem ,patch' von Ajuga reptans L. (Lamiaceae) Die räumliche klonale Struktur und die ,patch' Besiedlung von Ajuga reptans L. (Lamiaceae), einer häufigen Halbrosettenpflanze mit Ausläufern, wurden mit einem morpho-ökologischen und molekular-genetischen Ansatz kombiniert analysiert. Die Untersuchung wurde in einem ,patch' aus einem Wald bei Diedorf (Thüringen) durchgeführt: Morphologisch wurden Merkmale des klonalen Wachstums und der klonalen Reproduktion untersucht, die räumliche Verteilung der Module kartiert und Merigenet-Beziehungen rekonstruiert. Für Proben aus dem ,patch', aus dessen näherer Umgebung und einer Pflanze aus Berlin wurden AFLP Analysen mit vier verschiedenen Primer-Kombinationen durchgeführt, um genetische Individuen (Genets) zu identifizieren. Die meisten Unterschiede in den Fragmentmustern zeigten sich bereits zwischen Proben aus Diedorf. Die ,patch'-Proben (morphologisch aufgeteilt in drei "Pflanzen") hatten jedoch sehr ähnliche fingerprints, was ihre Zugehörigkeit zum selben Genet und eine klonale Abstammung belegt. Für eine Probe ließen sich die Verwandtschaftsbeziehungen mit den AFLP Daten nicht sicher klären. Der Abgleich mit den morphologischen Ergebnissen ermöglichte jedoch eine Interpretation, und deutet auf die Zugehörigkeit zum Klon. Die Bedeutung der "vegetativen Multiplikation" (durch klonales Wachstum und klonale Reproduktion) für die Besiedlung und dauerhafte Besetzung von ,patches' wird diskutiert. [source]

Hepatic progenitor cells, stem cells, and AFP expression in models of liver injury

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2006
Wolf D. Kuhlmann
Abstract Adult hepatocytes and liver-cell progenitors play a role in restoring liver tissue after injury. For the study of progenitor cells in liver repair, experimental models included (a) surgical removal of liver tissue by partial hepatectomy; (b) acute injury by carbontetrachloride; (c) acute injury by d -galactosamine (GalN) and N -nitrosomorpholine (NNM); and (d) chemical hepatocarcinogenesis by feeding NNM in low and high doses. Serological and immunohistological detection of alpha-fetoprotein gene expression served to follow pathways of cellular differentiation. Stem cells were not required in models of surgical removal of parenchyma and in carbon tetrachloride intoxication of adult hepatocytes. In contrast, regeneration of liver occurred through biliary epithelial cells in injuries induced by GalN and NNM. These biliary epithelial cells, collectively called oval cells, are most probably derived from the canals of Hering. Proliferating bile duct cells reached a level of differentiation with reactivation of foetal genes and significant alpha-1-fetoprotein (AFP) synthesis signalling a certain degree of retrodifferentiation with potential stemness. Due to the same embryonic origin of bile ducts and hepatocytes, biliary epithelium and its proliferating progeny (oval cells) have a defined role in liver regeneration as a transit and amplification compartment. In their early proliferation stage, oval cells were heavily engaged in DNA synthesis ([3H]thymidine labelling). Pulse-chase experiments during experimental hepatocarcinogenesis exhibited their development into hepatocytes with high risk for transformation and leading to foci of altered hepatocytes. Hepatocellular carcinomas may arise either from proliferating/differentiating oval cells or from adult hepatocytes; both cell types have stem-like properties. AFP-positive and AFP-negative carcinomas occurred in the same liver. They may represent random clonal origin. The heterogeneity of phenotypic marker (AFP) correlated with a process of retrodifferentiation. [source]

Coexistence of light chain disease and chronic lymphocytic leukaemia, a complex karyotype with a rapid fatal outcome

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2006
H. CASTRYCK
Summary We report on a 48-year-old man with concomitantly diagnosed kappa expressing chronic lymphocytic leukaemia (CLL) and lambda light chain disease with highly complex chromosomal aberrations. The clinical course of the disease was very aggressive with survival of only 1 month. We demonstrate the distinct clonal origin by cytogenetic data and immunoglobulin rearrangement studies. To our knowledge this is the first report of a light chain disease associated with CLL. [source]

Merkel cell (primary neuroendocrine) carcinoma of the skin with nodal metastasis showing rhabdomyosarcomatous differentiation

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2002
María-Teresa Fernández-Figueras
Background:, We describe a unique case of Merkel cell (primary neuroendocrine) carcinoma of the skin with a lymph node metastasis showing rhabdomyosarcomatous differentiation. Skeletal muscle differentiation has occasionally been described in primary small cell neuroendocrine carcinomas and considered a form of dual differentiation rather than a collision tumor. In the present case, capacity for divergent differentiation appeared late in the course of the tumor, which suggests a clonal origin for both components of the neoplasm. Conclusions:, The coexistence of neural and rhabdomyoblastic types of differentiation, best epitomized by the Triton tumor, has been construed as the product of dual differentiation of cells originated from neural crest-derived ectomesenchyme. Since Merkel cells seem to originate from a pluripotential primitive keratinocyte and not from the neural crest, rhabdomyoblastic differentiation in a metastasis of primary neuroendocrine carcinoma of the skin probably reflects the close proximity between the programs of neural and skeletal muscle differentiation, which would have been sequentially activated in the case we are reporting. [source]

Clonal nature of odontogenic tumours

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2009
Carolina Cavaliéri Gomes
Background:, Although clonal origin is an essential step in the comprehension of neoplasias, there have been no studies to examine whether odontogenic tumours are derived from a single somatic progenitor cell. The purpose of this study was to investigate the clonal origin of odontogenic tumours. Methods:, Fresh samples of seven ameloblastomas, two odontogenic mixomas, two adenomatoid odontogenic tumour, one calcifying odontogenic cyst, one calcifying epithelial odontogenic tumour (CEOT) and six odontogenic keratocyst (OKC) of female patients were included in this study. After DNA extraction, the HUMARA gene polymorphism assay was performed. Results:, Most of the informative odontogenic lesions studied (12 out of 16) showed a monoclonal pattern. Among the polyclonal cases, two were OKC, one CEOT and one odontogenic mixoma. Conclusions:, Our results suggest that most odontogenic tumours are monoclonal. [source]

New insights into the nature of Warthin's tumour

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2009
Iain David O'Neill
Warthin's tumour is considered heterogeneous as to its pathogenesis with some data supporting a polyclonal origin for the epithelium, implying a non-neoplastic nature. After inconsistent reports, current information from molecular studies suggests that a recurrent t(11;19) and associated CRTC1-MAML2 fusion oncogene characterizes a subset of Warthin's tumours and supports a clonal origin in such cases. CRTC1-MAML2 is also a frequent feature of mucoepidermoid carcinoma. These findings, and the recent reports of Warthin's tumour and co-existent mucoepidermoid carcinoma with common CRTC1-MAML2 expression, provide a morphological and molecular framework for future studies as a basis for a fresh appraisal of the pathogenesis of Warthin's tumour. The underlying molecular basis and the pivotal studies defining such events are discussed. [source]

EBV negative Richter's syndrome from a coexistent clone after salvage treatment with alemtuzumab in a CLL patient

AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2006
Ann Janssens
Abstract Transformation of B cell chronic lymphocytic leukemia (B-CLL) to large cell lymphoma or Hodgkin's disease is known as a Richter's syndrome (RS). According to the literature, 1,10% of B-CLL patients develop this high-grade lymphoid malignancy. The relationship between the immunosuppressive effect of nucleoside analogues (NA) and monoclonal antibodies and the development of large cell transformation still remains a controversial issue. We describe a CLL patient who developed a large B cell lymphoma 94 months after diagnosis and 3 months after the start of alemtuzumab. The CLL immunophenotype was retained by the transforming cells although a different light chain was expressed. Molecular analysis of the immunoglobulin heavy chain confirmed that the CLL and the RS had a different clonal origin. Subsequent molecular analyses of stored samples showed that the clone with transforming capacity already appeared two years before the clinical appearance of the RS. We hypothesize that alemtuzumab promoted the uncontrolled growth of the latest clone by eradicating the initial B-CLL clone efficiently, and by inducing a strong T cell depletion with consequent impairment of the immunosurveillance. We also ruled out that the RS was EBV driven. In conclusion, we report a case of EBV negative RS after alemtuzumab as salvage therapy. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source]

Statistical Tests for Clonality

BIOMETRICS, Issue 2 2007
Colin B. Begg
Summary Cancer investigators frequently conduct studies to examine tumor samples from pairs of apparently independent primary tumors with a view to determine whether they share a "clonal" origin. The genetic fingerprints of the tumors are compared using a panel of markers, often representing loss of heterozygosity (LOH) at distinct genetic loci. In this article we evaluate candidate significance tests for this purpose. The relevant information is derived from the observed correlation of the tumors with respect to the occurrence of LOH at individual loci, a phenomenon that can be evaluated using Fisher's exact test. Information is also available from the extent to which losses at the same locus occur on the same parental allele. Data from these combined sources of information can be evaluated using a simple adaptation of Fisher's exact test. The test statistic is the total number of loci at which concordant mutations occur on the same parental allele, with higher values providing more evidence in favor of a clonal origin for the two tumors. The test is shown to have high power for detecting clonality for plausible models of the alternative (clonal) hypothesis, and for reasonable numbers of informative loci, preferably located on distinct chromosomal arms. The method is illustrated using studies to identify clonality in contralateral breast cancer. Interpretation of the results of these tests requires caution due to simplifying assumptions regarding the possible variability in mutation probabilities between loci, and possible imbalances in the mutation probabilities between parental alleles. Nonetheless, we conclude that the method represents a simple, powerful strategy for distinguishing independent tumors from those of clonal origin. [source]