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At least 307 records · Page 17Linked to original sources
PubMed2007

Tiling resolution array comparative genomic hybridization analysis of a fibrosarcoma of bone.

Fibrosarcoma of bone is a rare malignant tumor accounting for less than 5% of all primary malignant bone neoplasms. There is very limited knowledge regarding the molecular genetics of this tumor, and there are no cytogenetic data available. In the present study, a fibrosarcoma deriving from the left iliac bone of a 10-year-old girl was characterized using cytogenetics, fluorescence in situ hybridization (FISH), and whole genome tiling resolution array comparative genomic hybridization (CGH). Cytogenetic and FISH analyses revealed a ring chromosome 6 as the sole acquired aberration, a finding corroborated by array CGH. The ring formation, however, did not result in any gain of genetic material. Nor did the breakpoints in 6p25 and 6q14 seem to affect any known gene loci in such a way that the ring formation could have resulted in the creation of a fusion gene or in the exchange of regulatory sequences. Thus, a reasonable interpretation of the pathogenetic significance of the ring formation would be that it resulted in the loss of one or more putative tumor suppressor gene loci distal to the two breakpoints.

Bone Neoplasms↗
PubMed2004

Investigation of chromosomal imbalance in human embryos using comparative genomic hybridization.

Studies of cleavage-stage human embryos using fluorescence in-situ hybridization (FISH) to identify sub-sets of chromosomes have indicated that the incidence of chromosomal abnormalities is high. Whole genome amplification (WGA) and comparative genomic hybridization (CGH) to investigate the full chromosome complement applied to a small number of human embryos suggested an even higher rate of abnormality. WGA and CGH were used to identify genomic imbalance in individual blastomeres from human embryos, and the results were correlated with FISH analysis of sibling blastomeres. Forty embryos were analysed; 17 (42.5%) had a normal diploid karyotype and 23 (57.5%) were abnormal, with a chromosome imbalance in one or more cells including three (7.5%) that had a chaotic chromosome complement. Of the abnormal embryos, only three showed consistent aneuploidy. FISH results obtained from sibling blastomeres were in agreement with the CGH results in all 22 of the embryos where both tests were informative. It is concluded that rates of meiotic aneuploidy in human embryos may be lower than previous estimates. The results indicate that chromosomally abnormal embryos were more likely to have arisen as a result of cultural artefact or inadequate cell cycle surveillance, rather than meiotic error.

Adult↗
PubMedDate not supplied

Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool.

Cancer typically results in loosened control over genomic integrity, resulting in alterations of the genome of cancer cells. Comparative genomic hybridization (CGH) is a method that can be used on DNA extracted from routinely fixed tissue to assess the entire genome for the presence of changes in DNA copy number. CGH analysis has revealed that melanoma differs from melanocytic nevi by the presence of frequent chromosomal aberrations. In contrast, melanocytic nevi typically show no chromosomal aberrations, or have a restricted set of alterations with basically no overlap to melanoma. These marked differences between aberration patterns in melanomas and melanocytic nevi can be exploited diagnostically to classify melanocytic tumors that are ambiguous based on histopathologic assessment. In addition to potential diagnostic applications, detailed analyses of recurrent aberrations can lead to the identification of genes relevant in melanocytic neoplasia.

Adult↗
PubMed2005

The latest buzz in comparative genomics.

A second species of fruit fly has just been added to the growing list of organisms with complete and annotated genome sequences. The publication of the Drosophila pseudoobscura sequence provides a snapshot of how genomes have changed over tens of millions of years and sets the stage for the analysis of more fly genomes.

Animals↗
PubMed2003

Prognostic value of genomic alterations in head and neck squamous cell carcinoma detected by comparative genomic hybridisation.

A total of 45 primary head and neck squamous cell carcinomas were analysed by comparative genomic hybridisation to identify regions of chromosomal deletion and gain. Multiple regions of copy number aberration were identified including gains affecting chromosomes 3q, 8q, 5p, 7q, 12p and 11q and deletion of material from chromosomes 3p, 11q, 4p, 5q, 8p, 10q, 13q and 21. Kaplan-Meier survival analysis revealed significant correlations between gain of 3q25-27 and deletion of 22q with reduced disease-specific survival. In addition, gain of 17q and 20q, deletion of 19p and 22q and amplification of 11q13 were significantly associated with reduced disease-free survival. A Cox proportional hazards regression model identified deletion of 22q as an independent prognostic marker. The data presented here provide further evidence that the creation of a genetically based tumour classification system will soon be possible, complementing current histopathological characterisation.

Biomarkers, Tumor↗
PubMed2002

Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization.

OBJECTIVES: Barrett's oesophagus is a pre-neoplastic lesion, which develops as a complication of chronic gastro-oesophageal reflux disease and predisposes the patient to oesophageal adenocarcinoma. Our aim was to characterize karyotypic changes that may occur during the progression of Barrett's metaplasia through low-grade dysplasia and high-grade dysplasia to adenocarcinoma. METHODS: The technique of comparative genomic hybridization was used to characterize genome-wide changes in biopsies from patients with low-grade dysplasia, low-grade dysplasia plus high-grade dysplasia, high-grade dysplasia or adenocarcinoma. Both fresh and archival material was examined. RESULTS: Comparative genomic hybridization revealed a large amount of widespread chromosome instability at the high-grade dysplasia stage. No significant chromosome changes were detectable by comparative genomic hybridization in patients with low-grade dysplasia. Karyotypic changes in the adenocarcinoma patients were more specific than those found in the high-grade dysplasia patients. Chromosome 4 was amplified most often in high-grade dysplasia and chromosome 8q was amplified most frequently in the adenocarcinomas. CONCLUSIONS: These data demonstrate that high-grade dysplasia is the stage exhibiting widespread chromosome instability, which is detectable by comparative genomic hybridization. This instability is undetectable in low-grade dysplasia. The chromosome variation seen at high-grade dysplasia may be the source of more specific karyotypes that progress to adenocarcinoma. Importantly, we have identified chromosome 4 amplification as being heavily involved in the initiation of Barrett's progression. Specific chromosome changes (4 and 8q) may represent important regions on which to focus attention in future studies, with a view to identifying diagnostic markers.

Adenocarcinoma↗
PubMed2002

Cytogenetic characterization of chromosomal rearrangement in a human vinblastine-resistant CEM cell line: use of comparative genomic hybridization and fluorescence in situ hybridization.

In order to identify genomic changes associated with drug-resistance acquisition, we performed R-banding karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization to compare a human T-cell lymphoblastic leukemia cell line, CEM-wild type, and a subline with resistance to vinblastine (CEM-VLB) and overexpressing P-glycoprotein. Comparative genomic hybridization analysis showed that the CEM-VLB cell line carried chemoresistance-associated chromosomal abnormalities (amplification of 7q11 approximately q22, losses of chromosomes 2, 3, 5, 9, 10, and 16, and deletion of 4q13 approximately qter). Fluorescence in situ hybridization identified an amplified 7q21 region translocated on the short arm of a chromosome 2. This region contained the MDR1 gene locus and probably neighboring genes, such as SRI or MDR3/ABCB4. According to previous reports, this chromosomal rearrangement occurred during drug selection and attested a resistance acquisition.

Antineoplastic Agents, Phytogenic↗
PubMed2007

Low-level genomic instability is a feature of papillary thyroid carcinoma: an array comparative genomic hybridization study of laser capture microdissected papillary thyroid carcinoma tumors and clonal cell lines.

CONTEXT: Previous chromosomal comparative genomic hybridization (CGH) studies of papillary thyroid carcinoma (PTC) have demonstrated a low prevalence of aberrations, with the majority of tumors showing no evidence of chromosomal instability. The technique of CGH can be optimized, however, using array CGH and laser capture microdissection to ensure pure cell populations for analysis. OBJECTIVE: To assess PTC using array CGH applied to laser capture microdissected tumor cells and pure cell cultures. DESIGN: Well-characterized PTC (known ret/PTC and BRAF mutation status), including samples from 5 tumors with classic morphology, 3 follicular variant tumors, and 3 clonal PTC cell lines, were analyzed. RESULTS: Copy gain and loss occurred in all of the tumor cases and cell lines examined. The most common recurrent aberrations involved gains on chromosomes 1, 5, 7, 11, 15, 17, and 22, with recurrent deletions occurring on chromosomes 4, 18, and 19. Analysis of the data from the 8 tumor samples showed that amplifications of TP73 (1p36.33), SNRPN (15q12), and PDGFB (22q13.1) occurred exclusively in tumors with a wild type BRAF. CONCLUSIONS: This study shows a higher prevalence of aberrations detected using array CGH allied to laser capture microdissection than previously described in the literature, and it appears that the combination of laser capture microdissection and arrayed clones optimizes studies utilizing CGH. Copy gain of PDGFB occurs in a subset of tumors showing no evidence of mutated BRAF or rearranged ret, suggesting that copy gain of PDGFB may underlie the increased expression of platelet-derived growth factor described recently in the literature.

Adult↗
PubMed2006

Comparison of chromosomal and array-based comparative genomic hybridization for the detection of genomic imbalances in primary prostate carcinomas.

BACKGROUND: In order to gain new insights into the molecular mechanisms involved in prostate cancer, we performed array-based comparative genomic hybridization (aCGH) on a series of 46 primary prostate carcinomas using a 1 Mbp whole-genome coverage platform. As chromosomal comparative genomic hybridization (cCGH) data was available for these samples, we compared the sensitivity and overall concordance of the two methodologies, and used the combined information to infer the best of three different aCGH scoring approaches. RESULTS: Our data demonstrate that the reliability of aCGH in the analysis of primary prostate carcinomas depends to some extent on the scoring approach used, with the breakpoint estimation method being the most sensitive and reliable. The pattern of copy number changes detected by aCGH was concordant with that of cCGH, but the higher resolution technique detected 2.7 times more aberrations and 15.2% more carcinomas with genomic imbalances. We additionally show that several aberrations were consistently overlooked using cCGH, such as small deletions at 5q, 6q, 12p, and 17p. The latter were validated by fluorescence in situ hybridization targeting TP53, although only one carcinoma harbored a point mutation in this gene. Strikingly, homozygous deletions at 10q23.31, encompassing the PTEN locus, were seen in 58% of the cases with 10q loss. CONCLUSION: We conclude that aCGH can significantly improve the detection of genomic aberrations in cancer cells as compared to previously established whole-genome methodologies, although contamination with normal cells may influence the sensitivity and specificity of some scoring approaches. Our work delineated recurrent copy number changes and revealed novel amplified loci and frequent homozygous deletions in primary prostate carcinomas, which may guide future work aimed at identifying the relevant target genes. In particular, biallelic loss seems to be a frequent mechanism of inactivation of the PTEN gene in prostate carcinogenesis.

Chromosome Aberrations↗
PubMed2006

Comparative genomics reveals unusually long motifs in mammalian genomes.

MOTIVATION: The recent discovery of the first small modulatory RNA (smRNA) presents the challenge of finding other molecules of similar length and conservation level. Unlike short interfering RNA (siRNA) and micro-RNA (miRNA), effective computational and experimental screening methods are not currently known for this species of RNA molecule, and the discovery of the one known example was partly fortuitous because it happened to be complementary to a well-studied DNA binding motif (the Neuron Restrictive Silencer Element). RESULTS: The existing comparative genomics approaches (e.g., phylogenetic footprinting) rely on alignments of orthologous regions across multiple genomes. This approach, while extremely valuable, is not suitable for finding motifs with highly diverged "non-alignable" flanking regions. Here we show that several unusually long and well conserved motifs can be discovered de novo through a comparative genomics approach that does not require an alignment of orthologous upstream regions. These motifs, including Neuron Restrictive Silencer Element, were missed in recent comparative genomics studies that rely on phylogenetic footprinting. While the functions of these motifs remain unknown, we argue that some may represent biologically important sites. AVAILABILITY: Our comparative genomics software, a web-accessible database of our results and a compilation of experimentally validated binding sites for NRSE can be found at http://www.cse.ucsd.edu/groups/bioinformatics.

Algorithms↗
PubMed2004

Library on a slide for bacterial comparative genomics.

BACKGROUND: We describe a novel application of microarray technology for comparative genomics of bacteria in which libraries of entire genomes rather than the sequence of a single genome or sets of genes are arrayed on the slide and then probed for the presence or absence of specific genes and/or gene alleles. RESULTS: We first adopted a 96-well high throughput working protocol to efficiently isolate high quality genomic DNA. We then optimized conditions to print genomic DNA onto a glass slide with high density (up to 15000 spots) and to sensitively detect gene targets in each genome spot using fluorescently labeled DNA probe. Finally, we created an E. coli reference collection array and probed it for the presence or absence of the hemolysin (hly) gene using a dual channel non-competing hybridization strategy. Results from the array hybridization matched perfectly with previous tests. CONCLUSIONS: This new form of microarray technology, Library on a Slide, is an efficient way for sharing and utilizing large strain collections in comparative genomic analyses.

Bacterial Typing Techniques↗
PubMed2002

Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization.

We have applied the method of genomic microarray to investigate amplification of oncogenes throughout the genome of nasopharyngeal carcinoma (NPC). Array based comparative genomic hybridization (array CGH) allows simultaneous examination of 58 oncogenes commonly amplified in various human cancers. In the present study, we have examined 15 NPC samples including five cell lines, two xenografts and eight primary tumours with array CGH to reveal the particular oncogenes associated with this cancer. This is the first genome wide survey of multiple oncogene amplifications involved in the development of NPC. Non-random gene amplifications were identified for the first time in NPC on MYCL1 in 1p34.3 and on TERC and PIK3CA at 3q26.3. Other high level amplified oncogenes included NRAS, RAF1, MYB, EGFR, FGF4, EMS1, and D17S167. Highest frequencies of gain of novel oncogenes were detected on MYCL1 (66.7%), TERC (46.7%), ESR (46.7%), PIK3CA (40%), LAMC2 (33.3%), and CSE1L (33.3%).

Carcinoma↗
PubMed2006

The impact of comparative genomics on infectious disease research.

The past decade has witnessed a revolution in infectious disease research, fuelled by the accumulation of a huge amount of DNA sequence data. The avalanche of genome sequence information has largely promoted the development of comparative genomics, which exploits available genome sequences to perform either inter- or intra-species comparisons of bacterial genome contents, or performs comparisons between the human genome and those of other organisms. This review aims to summarize how comparative genomics is being extensively used in infectious disease research, such as in the studies to identify virulence determinants, antimicrobial drug targets, vaccine candidates and new markers for diagnostics. These applications hold considerable promise for alleviating the burden of infectious diseases in the coming years.

Bacteria↗
PubMed2005

Distinct genomic profiles in hereditary breast tumors identified by array-based comparative genomic hybridization.

Mutations in BRCA1 and BRCA2 account for a significant proportion of hereditary breast cancers. Earlier studies have shown that inherited and sporadic tumors progress along different somatic genetic pathways and that global gene expression profiles distinguish between these groups. To determine whether genomic profiles similarly discriminate among BRCA1, BRCA2, and sporadic tumors, we established DNA copy number profiles using comparative genomic hybridization to BAC-clone microarrays providing <1 Mb resolution. Tumor DNA was obtained from BRCA1 (n = 14) and BRCA2 (n = 12) mutation carriers, as well as sporadic cases (n = 26). Overall, BRCA1 tumors had a higher frequency of copy number alterations than sporadic breast cancers (P = 0.00078). In particular, frequent losses on 4p, 4q, and 5q in BRCA1 tumors and frequent gains on 7p and 17q24 in BRCA2 tumors distinguish these from sporadic tumors. Distinct amplicons at 3q27.1-q27.3 were identified in BRCA1 tumors and at 17q23.3-q24.2 in BRCA2 tumors. A homozygous deletion on 5q12.1 was found in a BRCA1 tumor. Using a set of 169 BAC clones that detect significantly (P < 0.001) different frequencies of copy number changes in inherited and sporadic tumors, these could be discriminated into separate groups using hierarchical clustering. By comparing DNA copy number and RNA expression for genes in these regions, several candidate genes affected by up- or down-regulation were identified. Moreover, using support vector machines, we correctly classified BRCA1 and BRCA2 tumors (P < 0.0000004 and 0.00005, respectively). Further validation may prove this tumor classifier to be useful for selecting familial breast cancer cases for further mutation screening, particularly, as these data can be obtained using archival tissue.

Breast Neoplasms↗
PubMed2002

Compilation of published comparative genomic hybridization studies.

The power of comparative genomic hybridization (CGH) has been clearly proven since the first paper appeared in 1992 as a tool to characterize chromosomal imbalances in neoplasias. This review summarizes the chromosomal imbalances detected by CGH in solid tumors and in hemopathies. In May of 2001, we took a census of 430 articles providing information on 11,984 cases of human solid tumors or hematologic malignancies. Comparative generic hybridization has detected a number of recurrent regions of amplification or deletion that allows for identification of new chromosomal loci (oncogenes, tumor suppressor genes, or other genes) involved in the development, progression, and clonal evolution of tumors. When CGH data from different studies are combined, a pattern of nonrandom genetic aberrations appears. As expected, some of these gains and losses are common to different types of pathologies, while others are more tumor-specific.

Chromosome Aberrations↗
PubMed1999

Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals.

Comparative genomic hybridization (CGH) is a widely used technique for studying chromosomal imbalances. The sensitivity of the technique is, however, relatively low. Deletions down to a size of 10-12 Mbp have been detected by the use of fixed diagnostic thresholds. In this study, we applied standard reference intervals as detection criteria on a number of deletions in the range of 3 Mbp to 14-18 Mbp. All deletions were detected. Thus, detection by standard reference intervals confers a considerably higher sensitivity to CGH analysis compared to fixed diagnostic thresholds. Genes Chromosomes Cancer 25:410-413, 1999.

Chromosome Aberrations↗