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  • 1
    Keywords: PROGENITOR CELLS ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; NON-HODGKIN-LYMPHOMA ; SOMATIC MUTATIONS ; MONOCLONAL GAMMOPATHY ; B-CELL LYMPHOCYTOSIS ; HEALTHY-INDIVIDUALS ; UNDETERMINED SIGNIFICANCE MGUS ; SMOLDERING MULTIPLE-MYELOMA ; LOW-TUMOR-BURDEN
    Abstract: PURPOSE: The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL. PARTICIPANTS AND METHODS: Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t(14;18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t(14;18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples. RESULTS: Clonal analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t(14;18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t(14;18) prevalence and frequency than controls (P 〈 .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency 〉 10(-4) (odds ratio, 23.17; 95% CI, 9.98 to 67.31; P 〈 .001). Remarkably, risk estimates remained high and significant up to 15 years before diagnosis. CONCLUSION: High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis.
    Type of Publication: Journal article published
    PubMed ID: 24687831
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  • 2
    Keywords: CANCER ; BLOOD ; EPIDEMIOLOGY ; RISK-FACTORS ; FREQUENCY ; LYMPHOCYTES ; B-CELL LYMPHOMA ; NON-HODGKINS-LYMPHOMA ; SUBTYPES ; HEALTHY-INDIVIDUALS
    Abstract: PURPOSE: The strong association between t(14;18) translocation and follicular lymphoma (FL) is well known. However, the determinants of this chromosomal aberration and their role in t(14;18) associated FL remain to be established. METHODS: t(14;18) frequency within the B cell lymphoma 2 major breakpoint region was determined for 135 incident FL cases and 251 healthy controls as part of a nested case-control study within the European Prospective Investigation into Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from blood samples taken at recruitment. The relationship between prevalence and frequency of the translocation with baseline anthropometric, lifestyle, and dietary factors in cases and controls was determined. Unconditional logistic regression was used to explore whether the risk of FL associated with these factors differed in t(14;18)(+) as compared to t(14;18)(-) cases. RESULTS: Among incident FL cases, educational level (chi (2) p = 0.021) and height (chi (2) p = 0.025) were positively associated with t(14;18) prevalence, and cases with high frequencies [t(14;18)(HF)] were significantly taller (t test p value = 0.006). These findings were not replicated in the control population, although there were a number of significant associations with dietary variables. Further analyses revealed that height was a significant risk factor for t(14;18)(+) FL [OR 6.31 (95 % CI 2.11, 18.9) in the tallest versus the shortest quartile], but not t(14;18)(-) cases. CONCLUSIONS: These findings suggest a potential role for lifestyle factors in the prevalence and frequency of the t(14;18) translocation. The observation that the etiology of FL may differ by t(14;18) status, particularly with regard to height, supports the subdivision of FL by translocation status.
    Type of Publication: Journal article published
    PubMed ID: 26424368
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  • 3
    ISSN: 0273-1177
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2242
    Keywords: Key words Wheat ; High-molecular-weight glutenin ; AS-PCR ; Glu-A1 locus ; Null allele ; Triticum aestivum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The present work reports new PCR markers that amplify the complete coding sequence of the specific alleles of the high molecular weight (HMW) glutenin genes. A set of AS-PCR molecular markers was designed which use primers from nucleotide sequences of the Glu-A1 and Glu-D1 genes, making use of the minor diffeences between the sequences of the x1, x2* of Glu-A1, and the x5 and y10 of Glu-D1. These primers were able to distinguish between x2* and the x1 or xNull of Glu-A1. Also x5 was distinguishable from x2, and y10 from y12. The primers amplified the complete coding regions and corresponded to the upstream and downstream flanking positions of Glu-A1 and Glu-D1. Primers designed to amplify the Glu-A1 gene amplified a single product when used with genomic DNA of common wheats and the xNull allele of this gene. This work also describes the cloning and characterisation of the nucleotide sequence of this allele. It possesses the same general structure as x2* and x1 (previously determined) and differs from these alleles in the extension of the coding sequence for a presumptive mature protein with only 384 residues. This is due to the presence of a stop codon (TAA) 1215-bp downstream from the start codon. A further stop codon (TAG), 2280-bp downstream from the starting codon is also found. The open reading frame of xNull and x1 alleles has the same size in bp. Both are larger than x2* which shows two small deletions. The reduced size of the presumptive mature protein encoded by xNull could explain the negative effect of this allele on grain quality.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2242
    Keywords: C-banding ; Common wheat ; Triticum aestivum L. ; Translocations ; Heterochromatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The C-banding pattern of nine meiotic chromosomes of common wheat (Triticum aestivum L.) as described. In F1s of crosses between monosomics of ‘Chinese Spring’ and two Spanish wheat cultivars, univalent chromosomes were used to aid the recognition and analysis of the C-banding pattern for the individual chromosomes. The identification of one chromosome involved in one translocation in ‘Chinese Spring’ x ‘Pané 247’ has been made through heterochromatin bands observed in the chromosomes involved in multivalents.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 69 (1984), S. 193-198 
    ISSN: 1432-2242
    Keywords: C-banding ; Heterochromatin ; Meiosis ; Common wheat ; Triticum aestivum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The meiotic identification of nine pairs of chromosomes at metaphase I of meiosis of Triticum aestivum (B genome, 4A and 7A) has been achieved using a Giemsa C-banding technique. As a result, the analysis of the pairing of each chromosome arm in disomic and monosomic intervarietal hybrids between ‘Chinese Spring’ and the Spanish cultivar ‘Pané 247’ could be carried out. Differences in the chiasmata frequencies per chromosome arm cannot be explained on the basis of relative arm lengths only. Possible effects of arm-to-arm heterochromatic differences on meiotic pairing are discussed.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2242
    Keywords: Gliadin ; Two-dimensional electrophoresis ; F1 monosomic analysis ; chromosomal assignment ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The gliadin components from four bread wheat cultivars: Chinese Spring, Capelle Desprez, Holdfast and Pane-247 and their monosomic F1s for the chromosomes of homoeologous groups 1 and 6 have been analyzed by two-dimensional (2-pH) polyacrylamide gel electrophoresis. Chromosomal location of gliadin genes and the allelic differences were well established by analyzing the different F1 monosomic hybrids, electrophoretical patterns and differences in relative staining intensity. A new gliadin encoded by a gene located on chromosome 6B in Chinese Spring is described. The two-dimensional patterns of gliadin in the other three varieties and the chromosomal location of their genes are reported for the first time. Relationships between gliadins in the two-dimensional patterns and the traditional system for their nomenclature are discussed.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2242
    Keywords: Hordeum chilense ; Tritordeum ; Esterases ; Glutamate oxaloacetate transaminase ; Phosphoglucomutase ; Isozymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Polyacrylamide and starch gel electrophoresis of esterase (EST), glutamate oxaloacetate transaminase (GOT) and phosphoglucomutase (PGM) isozymes in Hordeum chilense, Triticum turgidum conv. durum, the amphiploid H. chilense X T. turgidum (Tritordeum), and the durum wheat/H. chilense monosomic addition lines revealed the chromosomal location of one EST locus, two GOT loci and one PGM locus. Loci Est-H ch1 and Got-H ch2 were found on chromosome 6Hch,Got-H ch3 on chromosome 3Hch, and Pgm-H ch1 on chromosome 4Hch. These results lend evidence for the assumed homoeology relationships between chromosomes of Triticeae species.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2242
    Keywords: Key words Hordeum ; Barley ; RAPD ; Variability ; Phylogeny ; DNA analyses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The genetic variation of 102 natural populations of wild barley growing in Spain was assessed using RAPDs (random amplified polymorphic DNA). The plant material included the annual species H. marinum subsp. marinum (22 populations) and subsp. gussoneanum (14), H. murinum subsp. murinum (7) and subsp. leporinum (35), and the perennial species H. bulbosum (17) and H. secalinum (7). Ten of the tested 64 arbitrary 10-mer primers amplified polymorphic DNA in all taxonomic units. Analyses was performed within and between populations, species and subspecies. The primers gave a total of 250 RAPD products. The level of polymorphism varied between taxonomic units depending on the primers employed and the plant reproductive system. In general, the most variable were the allogamous species H. secalinum and H. bulbosum and the autogamous H. marinum subsp. marinum. Among the amplified bands, 69 (27%) were shared by at least two different taxonomic units. The remaining bands were specific. The results demonstrate differences in the degree of similarity between taxonomic units. Jaccard’s similarity coefficients for interval measure within and between populations were used to produce a cluster diagram using the unweighted pair-group method (UPGMA). The different populations of the species and subspecies of Hordeum fell into three groups. The first group contained the populations belonging to both subspecies of H. marinum, plus those of H. secalinum. The populations of H. marinum subsp. gussoneanum were very closely associated. Those of H. marinum subsp. marinum were grouped in a broad cluster. The second group, occupying the innermost position of the tree, was very closely associated with the populations of both subspecies of H. murinum. The third branch segregated H. bulbosum. A series of RAPD markers were investigated by cleaving the amplified products of the same size with restriction endonucleases that recognize targets of 4- or 6-bp. The production of equivalent fragments following cleavage by the same enzyme would seem to demonstrate their homology in samples from different individuals, populations or taxonomic units.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2242
    Keywords: Key words Triticum aestivum L. ; Microsatellites ; C banding ; N banding ; Genome organization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Clusters of four simple sequence repeats (SSRs), AAC, AAG, AG and CAT, have been mapped physically to hexaploid wheat chromosomes; 15—24-bp synthetic oligonucleotides were labelled by random-primer labelling and used as probes for fluorescent in situ hybridization with standard formamide and low-salt conditions. AAC hybridized strongly to the pericentromeric regions and several intercalary sites of all seven chromosomes of the B-genome corresponding to N bands and enabling their identification. Most of the AAC sites also co-localize with AAG, although the strength of the AAC and AAG signal was often different at the same location. Not all heterochromatic bands showed AAC signals and a few AAC sites were detected that are neither AAG nor N band positive, revealing the complex and heterogeneous genome organization of wheat and identifying the four most frequent classes of banded chromatin. Clusters characterised by a high concentration of AG repeats were detected on chromosome arms 3BS, 4BL, 5BS and 5BL, adjacent to AAG sites. The only detectable CAT cluster was found on chromosome arm 3BL, making this oligonucleotide valuable in identifying this particular chromosome. SSR in situ hybridization is useful as a diagnostic tool in cytogenetics and for understanding genome organization in wheat.
    Type of Medium: Electronic Resource
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