Mapping of Multiple DNA Gains and Losses in Primary Small Cell Lung Carcinomas by Comparative Genomic Hybridization

Comparative genomic hybridization was applied for a comprehensive screening of under- and overrepresentation of genetic material in 13 autoptic small cell lung cancer specimens. The most abundant genetic changes include DNA losses of chromosome arms 3p, 5q, 10q, 13q, and 17p and DNA gains of 3q, 5p, 8q, and 17q. Amplification sites in these tumors were mapped to 22 chromosome bands. The most frequently involved band was 19q13.1 (4 cases). Bands 1p32, 2p23, 7q11.2, 8q24, and 13q33–34 were involved in two cases each

Symmetries of hadrons after unbreaking the chiral symmetry

We study hadron correlators upon artificial restoration of the spontaneously broken chiral symmetry. In a dynamical lattice simulation we remove the lowest lying eigenmodes of the Dirac operator from the valence quark propagators and study evolution of the hadron masses obtained. All mesons and baryons in our study, except for a pion, survive unbreaking the chiral symmetry and their exponential decay signals become essentially better. From the analysis of the observed spectroscopic patterns we conclude that confinement still persists while the chiral symmetry is restored. All hadrons fall into different chiral multiplets. The broken U(1)_A symmetry does not get restored upon unbreaking the chiral symmetry. We also observe signals of some higher symmetry that includes chiral symmetry as a subgroup. Finally, from comparison of the \Delta - N splitting before and after unbreaking of the chiral symmetry we conclude that both the color-magnetic and the flavor-spin quark-quark interactions are of equal importance.Comment: 12 pages, 14 figures; final versio

Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors by comparative genomic hybridization after universal DNA-amplification

We present a technique which allows the detection and chromosomal localization of DNA sequence copy number changes in solid tumor genomes from frozen sections and paraffin embedded, formalin fixed specimens. Based on comparative genomic hybridization and on universal DNA amplification procedures this technique is possible even if only a few tumor cells are available. We demonstrate the feasibility of this method to visualize complete and partial chromosome gains and losses and gene amplifications In archived solid tumor samples

Unbreaking chiral symmetry

In Quantum Chromodynamics (QCD) the eigenmodes of the Dirac operator with small absolute eigenvalues have a close relationship to the dynamical breaking of the chiral symmetry. In a simulation with two dynamical quarks, we study the behavior of meson propagators when removing increasingly more of those modes in the valence sector, thus partially removing effects of chiral symmetry breaking. We find that some of the symmetry aspects are restored (e.g., the masses of $\rho$ and $a_1$ approach each other) while confining properties persist.Comment: 5 pages, 5 figures (figure added, references updated

Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization

Comparative genomic in situ hybridization (CGH) provides a new possibility for searching genomes for imbalanced genetic material. Labeled genomic test DNA, prepared from clinical or tumor specimens, is mixed with differently labeled control DNA prepared from cells with normal chromosome complements. The mixed probe is used for chromosomal in situ suppression (CISS) hybridization to normal metaphase spreads (CGH-metaphase spreads). Hybridized test and control DNA sequences are detected via different fluorochromes, e.g., fluorescein isothiocyanate (FITC) and tetraethylrhodamine isothiocyanate (TRITC). The ratios of FITC/TRITC fluorescence intensities for each chromosome or chromosome segment should then reflect its relative copy number in the test genome compared with the control genome, e.g., 0.5 for monosomies, 1 for disomies, 1.5 for trisomies, etc. Initially, model experiments were designed to test the accuracy of fluorescence ratio measurements on single chromosomes. DNAs from up to five human chromosome-specific plasmid libraries were labeled with biotin and digoxigenin in different hapten proportions. Probe mixtures were used for CISS hybridization to normal human metaphase spreads and detected with FITC and TRITC. An epifluorescence microscope equipped with a cooled charge coupled device (CCD) camera was used for image acquisition. Procedures for fluorescence ratio measurements were developed on the basis of commercial image analysis software. For hapten ratios 4/1, 1/1 and 1/4, fluorescence ratio values measured for individual chromosomes could be used as a single reliable parameter for chromosome identification. Our findings indicate (1) a tight correlation of fluorescence ratio values with hapten ratios, and (2) the potential of fluorescence ratio measurements for multiple color chromosome painting. Subsequently, genomic test DNAs, prepared from a patient with Down syndrome, from blood of a patient with Tcell prolymphocytic leukemia, and from cultured cells of a renal papillary carcinoma cell line, were applied in CGH experiments. As expected, significant differences in the fluorescence ratios could be measured for chromosome types present in different copy numbers in these test genomes, including a trisomy of chromosome 21, the smallest autosome of the human complement. In addition, chromosome material involved in partial gains and losses of the different tumors could be mapped to their normal chromosome counterparts in CGH-metaphase spreads. An alternative and simpler evaluation procedure based on visual inspection of CCD images of CGH-metaphase spreads also yielded consistent results from several independent observers. Pitfalls, methodological improvements, and potential applications of CGH analyses are discussed