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71.
Ewa Przybytkowski Elizabeth Lenkiewicz Michael T Barrett Kathleen Klein Sheida Nabavi Celia MT Greenwood Mark Basik 《BMC genomics》2014,15(1)
Background
Chromosomal breakage followed by faulty DNA repair leads to gene amplifications and deletions in cancers. However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). We present here a novel approach to array CGH data analysis, which focuses on putative breakpoints responsible for rearrangements within the genome.Results
We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. The specimens were flow sorted according to ploidy to increase tumor cell purity prior to array CGH. We describe the number of chromosomal breaks as well as the patterns of breaks on individual chromosomes in each tumor. There were differences in chromosomal breakage patterns between the 3 clinical subtypes of breast cancers, although the highest density of breaks occurred at chromosome 17 in all subtypes, suggesting a particular proclivity of this chromosome for breaks. We also observed chromothripsis affecting various chromosomes in 41% of high risk breast cancers.Conclusions
Our results provide a new insight into the genomic complexity of breast cancer. Genomic instability dependent on chromosomal breakage events is not stochastic, targeting some chromosomes clearly more than others. We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-579) contains supplementary material, which is available to authorized users. 相似文献72.
Biosynthesis of sphingomyelin from erythro-ceramides and phosphatidylcholine by a microsomal cholinephosphotransferase 总被引:5,自引:0,他引:5
Mouse liver microsomes were shown to be active in the synthesis of sphingomyelin from ceramide and phosphatidylcholine in a reaction independent of CDPcholine. The conversion was not inhibited by calcium chelating reagents, and no evidence for the involvement of phospholipase C activity in the transformation could be adduced. Activity was also demonstrated in monkey liver and heart microsomes. Mouse brain microsomes produced a sphingomyelin analogue, tentatively identified as ceramide phosphorylethanolamine, but not sphingomyelin. Both [14C]ceramide and [G-14]phosphatidylethanolamine were precursors of the brain product, while phosphatidylcholine was inactive. Progress in the partial characterization of the liver enzyme is also described. 相似文献
73.
74.
Roberts SC Tancer MJ Polinsky MR Gibson KM Heby O Ullman B 《The Journal of biological chemistry》2004,279(22):23668-23678
The polyamine pathway of protozoan parasites has been successfully targeted in anti-parasitic therapies and is significantly different from that of the mammalian host. To gain knowledge into the metabolic routes by which parasites synthesize polyamines and their precursors, the arginase gene was cloned from Leishmania mexicana, and Deltaarg null mutants were created by double targeted gene replacement and characterized. The ARG sequence exhibited significant homology to ARG proteins from other organisms and predicted a peroxisomal targeting signal (PTS-1) that steers proteins to the glycosome, an organelle unique to Leishmania and related parasites. ARG was subsequently demonstrated to be present in the glycosome, whereas the polyamine biosynthetic enzymes, in contrast, were shown to be cytosolic. The Deltaarg knockouts expressed no ARG activity, lacked an intracellular ornithine pool, and were auxotrophic for ornithine or polyamines. The ability of the Deltaarg null mutants to proliferate could be restored by pharmacological supplementation, either with low putrescine or high ornithine or spermidine concentrations, or by complementation with an arginase episome. Transfection of an arg construct lacking the PTS-1 directed the synthesis of an arg that mislocalized to the cytosol and notably also complemented the genetic lesion and restored polyamine prototrophy to the Deltaarg parasites. This molecular, biochemical, and genetic dissection of ARG function in L. mexicana promastigotes establishes: (i) that the enzyme is essential for parasite viability; (ii) that Leishmania, unlike mammalian cells, expresses only one ARG activity; (iii) that the sole vital function of ARG is to provide polyamine precursors for the parasite; and (iv) that ARG is present in the glycosome, but this subcellular milieu is not essential for its role in polyamine biosynthesis. 相似文献
75.
76.
Stein A Vaseduvan G Carter NS Ullman B Landfear SM Kavanaugh MP 《The Journal of biological chemistry》2003,278(37):35127-35134
Leishmania donovani express two members of the equilibrative nucleoside transporter family; LdNT1 encoded by two closely related and linked genes, LdNT1.1 and LdNT1.2, that transport adenosine and pyrimidine nucleosides and LdNT2 that transports inosine and guanosine exclusively. LdNT1.1, LdNT1.2, and LdNT2 have been expressed in Xenopus laevis oocytes and found to be electrogenic in the presence of nucleoside ligands for which they mediate transport. Further analysis revealed that ligand uptake and transport currents through LdNT1-type transporters are proton-dependent. In addition to the flux of protons that is coupled to the transport reaction, LdNT1 transporters mediate a variable constitutive proton conductance that is blocked by substrates and dipyridamole. Surprisingly, LdNT1.1 and LdNT1.2 exhibit different electrogenic properties, despite their close sequence homology. This electrophysiological study provides the first demonstration that members of the equilibrative nucleoside transporter family can be electrogenic and establishes that these three permeases, unlike their mammalian counterparts, are probably concentrative rather than facilitative transporters. 相似文献
77.
78.
79.
Sweetpotato whitefly resistance to insecticides in Hawaii: Intra-island variation is related to insecticide use 总被引:1,自引:0,他引:1
A. D. Omer M. W. Johnson B. E. Tabashnik H. S. Costa D. E. Ullman 《Entomologia Experimentalis et Applicata》1993,67(2):173-182
Susceptibility to acephate, methomyl, and permethrin was determined with laboratory bioassays of field-collected adults from
15 populations of the B biotype of sweetpotato whitefly,Bemisia tabaci (Gennadius) (Homoptera:Aleyrodidae), from Hawaii. Comparisons at the LC50 showed up to 24-fold resistance to acephate, 18-fold resistance to methomyl, and 4-fold resistance to permethrin. Analysis
of variance showed significant intra-island variation in susceptibility to each insecticide, but no significant variation
among islands. Insecticide use varied from 4 to 103 insecticide sprays per site per season. Acephate and methomyl were used
more often than permethrin. The frequency of application and LC50 for each insecticide were positively correlated across sites. These results suggest that local variation in insecticide use
was a primary cause of variation in susceptibility. If local insecticide use is a key determinant of resistance, as our results
suggest, growers can retard resistance development locally by reducing their own insecticide use. 相似文献
80.
A quantitative high performance liquid chromatography method for the analysis of neutral glycosylceramides as their perbenzoyl derivatives has been devised. Samples containing more than 2.5 nmol each of mono-, di-, tri-, and tetraglycosylceramide are benzoylated with 10% benzoyl chloride in pyridine at 37degrees C for 16 hr. The products are separated from excess reagents by solvent distribution and injected onto a pellicllar silica gel (Zipax) column (2.1 mm X 50 cm). The derivatives are eluted with a 10 min linear gradient of 2-17% ethyl acetate in hexane at 2 ml/min and absorbance at 280 nm is recorded. The detector response was proportional to the weight of sample used (2-30 nmol) and the lower limit of detection was about 70 pmol. The procedure has been applied to the quantitative analysis of erythrocyte and plasma glycolipids. As little as 0.5 ml of plasma can be used for analysis. The relative standard deviation of repetitive analyses ranged between 2.0% for glucosylceramide to 5.4% for galactosyllactosylceramide. 相似文献