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Chromosomal Arms (chromosomal + arm)
Selected AbstractsFrequent high telomerase reverse transcriptase expression in primary oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2007Kolja Freier Background:, Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC. Methods:, Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC). Results:, Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P < 0.001). By contrast, specific TERT amplifications were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P = 0.047). Conclusions:, High hTERT expression is a frequent finding in OSCC. It might be a promising target for the development of specific anti-neoplastic therapy approaches. [source] High throughput comparative genomic hybridization array analysis of multifocal urothelial cancersCANCER SCIENCE, Issue 8 2006Hiroaki Kawanishi The purpose of this study was to examine genetic alterations occur during synchronous or metachronous multifocal development of urothelial cancers on the whole genome using a comparative genomic hybridization (CGH) array. We used 10 tumor pairs (2 tumors for each patient), in which we had previously defined a clonal relationship by microsatellite analysis. For CGH array analysis, Vysis GenoSensor Array 300 kit was used. An unsupervised hierarchical cluster analysis revealed that the tumors from one patient were clustered together independent of the tumors of all other patients. On the other hand, many genetic divergences among multifocal urothelial cancers were newly found by a CGH array analysis. The concordant genetic alteration patterns of the chromosomal arm in tumor pairs were most frequently observed in 9p, 9q, 8p, 7p, 7q and 11q, while discordant patterns were most frequently found in 15q, 20q, 2q, 10p and 11q. Investigation using a CGH array showed that genetically stable multifocal tumors were less frequent, and that a large percentage of urothelial cancers accumulate genetic alterations during multifocal development by clonal evolution. We might have to consider these genetic accumulations during multifocal development when designing strategies for prevention and detection of recurrent multifocal urothelial cancers. CGH array can be a powerful tool for genetic analysis of multifocal urothelial cancer. (Cancer Sci 2006; 97: 746,752) [source] Genome-wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic lossGENES, CHROMOSOMES AND CANCER, Issue 3 2003D. J. Simpson Through the use of a candidate gene approach, several previous studies have identified loss of heterozygosity (LOH) at putative tumor-suppressor gene (TSG) loci in sporadic pituitary tumors. This study reports a genome-wide allelotyping by use of 122 microsatellite markers in a large cohort of tumors, consisting of somatotrophinomas and non-functioning adenomas. Samples were first subject to prior whole genome amplification by primer extension pre-amplification (PEP) to circumvent limitations imposed by insufficient DNA for whole-genome analysis with this number of microsatellite markers. The overall mean frequency of loss in invasive tumors was significantly higher than that in their non-invasive counterparts (7 vs. 3% somatotrophinomas; 6 vs. 3% non-functioning adenomas, respectively). Analysis of the mean frequency of LOH, across all markers to individual chromosomal arms, identified 13 chromosomal arms in somatotrophinomas and 10 in non-functioning tumors, with LOH greater than the 99% upper confidence interval calculated for the rate of overall random allelic loss. In the majority of cases, these losses were more frequent in invasive tumors than in their non-invasive counterparts, suggesting these to be markers of tumor progression. Other regions showed similar frequencies of LOH in both invasive and non-invasive tumors, implying these to be early changes in pituitary tumorigenesis. This genome-wide study also revealed chromosomal regions where losses were frequently associated with an individual marker, for example, chromosome arm 1q (LOH > 30%). In some cases, these losses were subtype-specific and were found at a higher frequency in invasive tumors than in their non-invasive counterparts. Identification of these regions of loss provides the first preliminary evidence for the location of novel putative TSGs involved in pituitary tumorigenesis that are, in some cases, subtype-specific. This investigation provides an unbiased estimate of global aberrations in sporadic pituitary tumors as assessed by LOH analysis. The identification of multiple "hotspots" throughout the genome may be a reflection of an unstable chromatin structure that is susceptible to a deletion or epigenetic-mediated gene-silencing events. © 2003 Wiley-Liss, Inc. [source] Clear-cell adenofibroma can be a clonal precursor for clear-cell adenocarcinoma of the ovary: a possible alternative ovarian clear-cell carcinogenic pathway,THE JOURNAL OF PATHOLOGY, Issue 1 2008S Yamamoto Abstract Several studies have reported that ovarian clear-cell adenocarcinoma can be derived from endometriosis. Although the clear-cell adenofibroma (CCAF), a major form of benign and borderline ovarian clear-cell tumour, has been suggested as another precursor for clear-cell adenocarcinoma (CCA), there is no supportive genetic evidence for this presumption. To examine the genetic linkage between CCAF and CCA of the ovary, we conducted allelotype analysis for both CCAF and adjacent CCA components in 14 cases of CCA associated with benign CCAF and/or borderline CCAF. DNA isolated from laser-microdissected tissue was subjected to polymerase chain reaction and analysis for loss of heterozygosity (LOH), using 17 polymorphic markers located on 11 chromosomal arms: 1p, 5q, 8p, 9p, 9q, 10q, 11q, 13q, 18q, 19p and 22q. For all informative loci, the frequency of LOH in adenocarcinoma was 49% (54/110 loci), and was significantly higher than those in the components of benign CCAF (22%, 20/92 loci) and borderline CCAF (30%, 25/83 loci) (,2 test; p < 0.05, respectively). The concordance rate in allelic patterns at all informative loci was 74% between benign CCAF and adenocarcinoma components, 81% between borderline CCAF and adenocarcinoma components, and 95% between benign CCAF and borderline CCAF components. Furthermore, between CCAF and adenocarcinoma components, an identical LOH pattern, involving the same alleles, was found in 13 (93%) of 14 cases at one or more chromosomal loci, and estimation of probability indicated that these events were very unlikely to have occurred by chance. Among the markers examined, LOHs on 5q, 10q and 22q were frequent in both CCAF and adenocarcinoma components, whereas LOHs on 1p and 13q were rare in CCAF components but frequent in adenocarcinoma components. These findings suggest that CCAF can be a clonal precursor for ovarian clear-cell adenocarcinoma. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Macro-Anatomical and Karyological Features of Two Blind Mole Rat Subspecies (Rodentia: Spalacidae) from TurkeyANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2009T. Kankiliç Summary The morphometric and karyological analyses of 52 specimens belonging to the two subspecies of Nannospalax leucodon were examined from 14 localities in Turkey. Five karyotypic forms were recorded (2n = 60, the total numbers of chromosomal arms (NF) = 74, the numbers of autosomal arms (NFa) = 70; 2n = 60, NF = 76, NFa = 72; 2n = 60, NF = 82, NFa = 78; 2n = 56, NF = 72, NFa = 68; 2n = 38, NF = 74, NFa = 70). The morphological features of two subspecies were studied using both numerical taxonomy and traditional methods. Thirty skull measurements and four baculum measurements were subjected to discriminant function analysis to find morphometric criteria allowing subspecies identification. Two subspecies were clearly separated from each other by macroanatomical characterictics and numeric characteristics. The first upper molar has four alveoli cubicles in young specimens of Nannospalax leucodon anatolicus, while M1 has 1 cubicle in Nannospalax leucodon cilicicus. In the western subspecies (N. l. anatolicus, 2n = 38), urethra openness is surrounded by three lobes. However, in the eastern subspecies (N. l. cilicicus, 2n = 60), there are two lateral lobes. [source] Statistical Tests for ClonalityBIOMETRICS, Issue 2 2007Colin 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] Integrated genomic and expression profiling in mantle cell lymphoma: identification of gene-dosage regulated candidate genesBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2008Margit Schraders Summary Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) translocation and several other cytogenetic aberrations, including heterozygous loss of chromosomal arms 1p, 6q, 11q and 13q and/or gains of 3q and 8q. The common intervals of chromosomal imbalance have been narrowed down using array-comparative genomic hybridization (CGH). However, the chromosomal intervals still contain many genes potentially involved in MCL pathogeny. Combined analysis of tiling-resolution array-CGH with gene expression profiling on 11 MCL tumours enabled the identification of genomic alterations and their corresponding gene expression profiles. Only subsets of genes located within given cytogenetic anomaly-intervals showed a concomitant change in mRNA expression level. The genes that showed consistent correlation between DNA copy number and RNA expression levels are likely to be important in MCL pathology. Besides several ,anonymous genes', we also identified various fully annotated genes, whose gene products are involved in cyclic adenosine monophosphate-regulated pathways (PRKACB), DNA damage repair, maintenance of chromosome stability and prevention of rereplication (ATM, ERCC5, FBXO5), energy metabolism (such as genes that are involved in the synthesis of proteins encoded by the mitochondrial genome) and signal transduction (ARHGAP29). Deregulation of these gene products may interfere with the signalling pathways that are involved in MCL tumour development and maintenance. [source] | ||||||||||