SEARCH · PubMed Health

Results for “Comparative Genomic Hybridization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1995

[Detection of DNA amplifications and deletions in oral squamous cell carcinoma cell lines by comparative genomic hybridization (CGH)].

Comparative genomic hybridization (CGH) has recently developed for surveying DNA sequence copy number in tumors. The purpose of this study is to find and map chromosomal regions with amplifications and deletions in oral cancers by CGH. The results were further compared to those obtained by Southern hybridization and fluorescence in situ hybridization to investigate the mechanism of CGH identifying the amplification of oncogenes. DNAs extracted from 17 oral squamous cell carcinoma cell lines were labeled with biotin and hybridized to a normal metaphase spread together with digoxigenin-labeled normal reference DNA. The relative intensities of tumor DNA (detected using FITC) and normal DNA (detected with rhodamine) were measured by fluorescence imaging analysis system. Recurrent loci for amplification were observed on 8q22-q26, 3q25-q27, 7p12, 11q13, 13q33, 14q, 15q and 20q13. Deletions were seen on 3p, 18q21, 5q21-q22, 7q31 and 8p. There was a strong concordance for amplification detected by the CGH and Southern hybridization methods. These results indicated that these loci may contain previously unknown genes. Thus, CGH provides a useful approach for rapid identification of putative oncogenes as well as finding specific genetic markers for oral cancers.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Chromosomal localization of DNA amplifications in neuroblastoma tumors using cDNA microarray comparative genomic hybridization.

Conventional comparative genomic hybridization (CGH) profiling of neuroblastomas has identified many genomic aberrations, although the limited resolution has precluded a precise localization of sequences of interest within amplicons. To map high copy number genomic gains in clinically matched stage IV neuroblastomas, CGH analysis using a 19,200-feature cDNA microarray was used. A dedicated (freely available) algorithm was developed for rapid in silico determination of chromosomal localizations of microarray cDNA targets, and for generation of an ideogram-type profile of copy number changes. Using these methodologies, novel gene amplifications undetectable by chromosome CGH were identified, and larger MYCN amplicon sizes (in one tumor up to 6 Mb) than those previously reported in neuroblastoma were identified. The genes HPCAL1, LPIN1/KIAA0188, NAG, and NSE1/LOC151354 were found to be coamplified with MYCN. To determine whether stage IV primary tumors could be further subclassified based on their genomic copy number profiles, hierarchical clustering was performed. Cluster analysis of microarray CGH data identified three groups: 1) no amplifications evident, 2) a small MYCN amplicon as the only detectable imbalance, and 3) a large MYCN amplicon with additional gene amplifications. Application of CGH to cDNA microarray targets will help to determine both the variation of amplicon size and help better define amplification-dependent and independent pathways of progression in neuroblastoma.

Algorithms↗

PubMed2005

SW-ARRAY: a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data.

Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267-1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides.

Algorithms↗

PubMed2005

Deletion at chromosome band 20p12.1 in colorectal cancer revealed by high resolution array comparative genomic hybridization.

Array comparative genomic hybridization (Array CGH) with tiling path resolution for a approximately 4.61 Mb region of chromosome band 20p12.1 has been used to investigate copy number loss in 48 colorectal cancer cell lines and 37 primary colorectal cancers. A recurrent deletion was detected in 55% of cell lines and 23% of primary cancers and the consensus minimum region of loss was identified as a approximately 190 kb section from 14.85 Mb to 15.04 Mb of chromosome 20. Two noncoding RNA genes located in the region, BA318C17.1 and DJ974N19.1, were investigated by mutation analysis and real-time PCR in colorectal cancer cell lines. Sequence changes in BA318C17.1 and reduced expression of both genes was detected, suggesting that the abrogation of these genes may play a role in colorectal tumorigenesis.

Cell Line, Tumor↗

PubMedDate not supplied

Meta-analysis and pooled re-analysis of copy number changes in colorectal cancer detected by comparative genomic hybridization.

BACKGROUND: Comparative genomic hybridization (CGH) provides an insight into chromosomal changes associated with colorectal cancer (CRC) development. However, a problem with many studies is the limited cohort size, making the significance of some findings unclear. MATERIALS AND METHODS: To derive a better insight into the chromosomal changes associated with CRC, we performed a meta-analysis and pooled re-analysis of published metaphase CGH data. RESULTS: In addition to recurrent alterations, gains of 20 13q, 8q and 7p and loss of 18, 17p, 8p and 4p, pooling identified less frequent, but significant changes, including gain of 1q and 3, and losses from 6q, 9p and 21q. CONCLUSION: These additional alterations may be characteristic of some tumors and thus have relevance to CRC biology. Meta-analysis not only has the potential to detect novel changes, present at low frequency in several independent studies, but can provide greater reliability for their detection than single studies alone.

Adenoma↗

PubMed1997

Objective aneuploidy detection for fetal and neonatal screening using comparative genomic hybridization (CGH).

Comparative genomic hybridization (CGH) allows entire genomes to be scanned for whole and segmental aneuploidy and thus may be an appropriate tool for the detection of clinically important abnormalities during fetal and neonatal screening. Criteria to distinguish between significant aberrations and experimental artifacts are essential for these applications. This report describes the use of a t-statistic to detect changes in CGH profiles that differ significantly from variations that occur in CGH profiles of normal samples. Eleven cell lines derived from fetal or neonatal patients were analyzed in this study. Aneuploidies in these lines included trisomies for chromosomes 13, 16, 18, and 21 and monosomy for distal 5p and tetrasomy 18p. Aneuploidy was detected in all samples by using the t-statistic, although the extent of the aneuploid region was not correctly estimated in some cases. A detailed description of the t-statistic fused for making these CGH comparisons is described in a companion paper (Moore et al., Cytometry 28:183-190, 1997.

Aneuploidy↗

PubMed2002

Frequent genomic imbalances in chromosomes 17, 19, and 22q in peripheral nerve sheath tumours detected by comparative genomic hybridization analysis.

Comparative genomic hybridization (CGH) was used to detect changes in relative chromosome copy number in 50 cases of peripheral nerve sheath tumour (PNSTs), including nine malignant peripheral nerve sheath tumours (MPNSTs), 27 neurofibromas (with three plexiform neurofibromas) and 14 schwannomas. Chromosome imbalances were frequently detected in benign as well as malignant PNSTs. In both NF1-associated and sporadic MPNSTs, the number of gains was higher than the number of losses, suggesting proto-oncogene activation during MPNST progression. NF1-asociated MPNSTs exhibited gains of chromosomes 17q and X (2/4 cases each), whereas sporadic MPNSTs showed gains of chromosome 4q (3/5 cases). On the other hand, in benign neurofibromas and schwannomas, the number of losses was higher than the number of gains, suggesting a predominant role of tumour suppressor genes in tumourigenesis. Both sporadic and NF1-associated neurofibromas exhibited losses at chromosome 22q in more than 50% of cases. These chromosomal regions may contain common chromosomal abnormalities characteristic of both types of neurofibromas. In NF1-associated neurofibromas, most frequent losses were found in chromosomes 17 [17p11.2-p13 in nine cases (60%); 17q24-25 in 6 cases (40%)] and 19 [19p13.2 in eight cases (53%); 19q13.2-qter in eight cases (53%)], whereas in sporadic neurofibromas and schwannomas losses of chromosomes 17 and 19 were detected in less than 50% of cases. Since this 17p11.2-p13 region is known to contain the tumour suppressor gene TP53, patients with NF1 may be at high risk of malignant neoplasms including MPNSTs. Gains were more frequently detected in plexiform neurofibromas (2/3 cases) than other benign tumours, suggesting proto-oncogene activation in tumourigenesis of plexiform neurofibroma. The significance of the losses of chromosome 19 in these cases is not clear at present, but in NF1-associated neurofibromas, the presence of some as yet unknown tumour suppressor genes on chromosome 19 cannot be ruled out.

Adolescent↗

PubMed2001

Identification and analysis of sex chromosomes by comparative genomic hybridization (CGH).

Comparative Genome Hybridization (CGH) can be used as a universal method for the identification of molecularly differentiated sex chromosomes. This is profitable in species with homomorphic sex chromosomes or when chromosomes are unfavourable for cytogenetics, e.g. when size differences are insufficient, chromosomes numerous and/or banding methods fail. In this method, genomic DNA from females competes as a probe with that from males for binding to the chromosome targets. Easy extraction and labelling methods afford a method that can be applied even when few specimens are available, e.g. when specimens for investigation have to be collected in the field - CGH also offers the possibility to obtain a rough estimate of the DNA composition of the sex chromosome.

Animals↗

PubMedDate not supplied

Clinical applications of comparative genomic hybridization.

PURPOSE: Comparative genomic hybridization (CGH) is a powerful DNA-based cytogenetic technique that allows the entire genome to be scanned for chromosomal imbalances without requiring the sample material to be mitotically active. During the past 2 years we received many requests from various medical centers around the country to use CGH to resolve the identity of aberrant chromosomal material. METHODS: We report the use of CGH for the evaluation of 12 clinical postnatal cases in which traditional cytogenetic analysis yielded ambiguous results. This series consisted of five marker chromosomes, five unbalanced translocations, and two intrachromosomal duplications. RESULTS: Identification and characterization of the additional unknown chromosomal material was achieved with use of CGH. All CGH findings were validated by traditional fluorescence in situ hybridization and other specialized staining techniques. CONCLUSLONS: These results demonstrate the effective use of CGH as a focused, single-step method for the identification of chromosomal material of unknown origin.

Adolescent↗

PubMed1997

Automatic correction of the interfering effect of unsuppressed interspersed repetitive sequences in comparative genomic hybridization analysis.

Comparative genomic hybridization (CGH) is a relatively new technique whose application is increasing. The method has mostly been employed for detection of chromosome aberrations in cancers, and a large amount of data in this field is accumulating. At the same time, efforts are made to improve the technique in order to increase the sensitivity and the generation of reliable results. Based on experimental data, we have developed a computer algorithm for eliminating some of the interfering effects of unsuppressed repetitive sequences in CGH analysis, and thereby improved our CGH analysis system.

Algorithms↗

PubMed2001

Complete karyotype characterization of the K562 cell line by combined application of G-banding, multiplex-fluorescence in situ hybridization, fluorescence in situ hybridization, and comparative genomic hybridization.

This study combines conventional cytogenetics, fluorescence in situ hybridization (FISH), multiplex-FISH and comparative genomic hybridization (CGH). In applying this multimodal approach on the human leukemia cell line K562, the chromosome composition was refined in detail and compared with data from the literature. A hypotriploid karyotype with a modal chromosome number of 67, and 21 unique marker chromosomes were identified. The classification of six markers was identical to published data and the composition of five further markers from the literature could be fully clarified for the first time. The composition of another five markers, which have been interpreted in divergent ways in different studies, were elucidated without doubt. Finally, five new markers of our study seem to have no equivalents in former studies, very likely due to limitations of conventional cytogenetics. The combinatory application of complementary techniques as shown in this study will be very useful to provide the basis of a refined genotype analysis on the chromosomal level.

Chromosome Mapping↗

PubMed1999

Effect of bone decalcification procedures on DNA in situ hybridization and comparative genomic hybridization. EDTA is highly preferable to a routinely used acid decalcifier.

Decalcification is routinely performed for histological studies of bone-containing tissue. Although DNA in situ hybridization (ISH) and comparative genomic hybridization (CGH) have been successfully employed on archival material, little has been reported on the use of these techniques on archival decalcified bony material. In this study we compared the effects of two commonly used decalcifiers, i.e. , one proprietary, acid-based agent (RDO) and one chelating agent (EDTA), in relation to subsequent DNA ISH and CGH to bony tissues (two normal vertebrae, six prostate tumor bone metastases with one sample decalcified by both EDTA and RDO). We found that RDO-decalcified tissue was not suited for DNA ISH in tissue sections with centromere-specific probes, whereas we were able to adequately determine the chromosomal status of EDTA-decalcified material of both control and tumor material. Gel electrophoresis revealed that no DNA could be successfully retrieved from RDO-treated material. Moreover, in contrast to RDO-decalcified tumor material, we detected several chromosomal imbalances in the EDTA-decalcified tumor tissue by CGH analysis. Furthermore, it was possible to determine the DNA ploidy status of EDTA- but not of RDO-decalcified material by DNA flow cytometry. Decalcification of bony samples by EDTA is highly recommended for application in DNA ISH and CGH techniques.

Bone Neoplasms↗

PubMed2001

Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.

Cytogenetic analysis of Bednar tumor (pigmented dermatofibrosarcoma protuberans) has not been reported previously. Here, we report the identification of a supernumerary ring chromosome in a Bednar tumor by chromosome painting with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Chromosome painting with FISH demonstrated that the supernumerary ring chromosome was composed of discontinuous, interwoven sequences from chromosomes 17 and 22. Amplification of chromosomes 17 and 22 sequences was confirmed by CGH. These results indicate that Bednar tumor and dermatofibrosarcoma protuberans are characterized by the same chromosomal features. To our knowledge, this is the first report that the ring chromosome in Bednar tumor is composed of amplified material from chromosomes 17 and 22.

Chromosome Banding↗

PubMed1997

Use of fluorescence in situ hybridization and comparative genomic hybridization in the cytogenetic analysis of testicular germ cell tumors and uveal melanomas.

Fluorescence in situ hybridization (FISH) with specific DNA probes and comparative genomic hybridization (CGH) are molecular cytogenetic methods that provide powerful supplementations of classical cancer cytogenetics. We present two examples of successful application of these new techniques in solid tumors in which basic information about specific cytogenetic aberrations had been gained previously by conventional karyotyping. In the first, testicular germ cell tumors (TGCT), FISH analysis allowed further characterization of the i(12p) marker chromosome. By CGH, chromosomal subregions that may harbor genes important for tumorigenesis or progression could be identified. In the second, uveal melanoma, CGH enabled a retrospective study in which monosomy 3 was statistically proved to be a relevant marker for poor prognosis.

Chromosome Deletion↗

PubMed2005

Characterization of chromosome 14 abnormalities by interphase in situ hybridization and comparative genomic hybridization in 124 meningiomas: correlation with clinical, histopathologic, and prognostic features.

We analyzed quantitative chromosome 14 abnormalities in 124 meningiomas by interphase fluorescence in situ hybridization (iFISH) and confirmed the nature of abnormalities by comparative genomic hybridization (CGH). We correlated the abnormalities with clinical, histopathologic, and prognostic factors. Of 124 cases, 50 (40.3%) showed loss (14.5%) or gain (25.8%) of the 14q32 chromosome region by iFISH. Most corresponded to numeric abnormalities: monosomy (12.9%), trisomy (1.6%), or tetrasomy (24.2%); in only 2 cases (1.6%), chromosome 14 loss did not involve the whole chromosome and was restricted to the 14q31-q32 region (confirmed by CGH). Cases with gain or monosomy corresponded more frequently to histologically malignant tumors (P = .009). Patients with monosomy 14/14q-, but not those with gain, more often were male (P = .04) and had a greater incidence of recurrence (P = .003) and shorter relapse-free survival (P = .03). The 2 patients with loss limited to 14q31-q32 had histologically benign tumors and no relapse after more than 5 years' follow-up. Most meningiomas with chromosome 14 abnormalities have numeric changes, with interstitial deletions of 14q31-q32 present in few cases. Of the abnormalities detected, only monosomy 14 showed an adverse prognostic impact.

Adolescent↗

PubMed1999

Comparative analysis of G-banding, chromosome painting, locus-specific fluorescence in situ hybridization, and comparative genomic hybridization in chronic myeloid leukemia blast crisis.

The molecular basis for blast transformation of chronic myeloid leukemia (CML) remains poorly understood. Cytogenetic alterations associated with CML blast crisis have previously been extensively studied by conventional G-banding analysis. However the complexity of some chromosome abnormalities or poor chromosome morphology or both has exceeded the resolution of G-banding analysis in a significant proportion of CML cases, and complex chromosome rearrangements have remained unidentified. In this study, comparative genomic hybridization (CGH) was used to elucidate genome imbalances in chronic phase or blast crisis samples or both from 12 CML patients. CGH and G-banding results were compared, and discrepancies were further clarified by using multipaint chromosome analysis and locus-specific DNA probes. No imbalances were detected in the 4 early disease phase samples studied. Eleven blast crisis samples were analyzed by G-banding and CGH, and the commonest genomic abnormality detected was overrepresentation of the long arm of chromosome 8, which was detected in 5 patients. This overrepresentation was attributable to trisomy 8 in 4 patients, whereas amplification of the entire long arm of chromosome 8 was detected in 1 patient. The formation of isochromosomes of the long arm of chromosome 8 was observed as a mechanism for gene amplification in this patient. Additional material originating from chromosome 8 was also observed intercalated into three marker chromosomes in peripheral blood metaphase spreads from this patient. These markers may further define areas on chromosome 8 that harbor oncogenes implicated in transformation of chronic myeloid leukemia.

Adolescent↗

PubMed2002

Physical mapping of genes in somatic cell radiation hybrids by comparative genomic hybridization to cDNA microarrays.

BACKGROUND: Somatic cell mutants can be informative in the analysis of a wide variety of cellular processes. The use of map-based positional cloning strategies in somatic cell hybrids to analyze genes responsible for recessive mutant phenotypes is often tedious, however, and remains a major obstacle in somatic cell genetics. To fulfill the need for more efficient gene mapping in somatic cell mutants, we have developed a new DNA microarray comparative genomic hybridization (array-CGH) method that can rapidly and efficiently map the physical location of genes complementing somatic cell mutants to a small candidate genomic region. Here we report experiments that establish the validity and efficacy of the methodology. RESULTS: CHO cells deficient for hypoxanthine:guanine phosphoribosyl transferase (HPRT) were fused with irradiated normal human fibroblasts and subjected to HAT selection. Cy5-labeled genomic DNA from the surviving hybrids containing the HPRT gene was mixed with Cy3-labeled genomic DNA from normal CHO cells and hybridized to a microarray containing 40,185 cDNAs, representing 29,399 genes (UniGene clusters). The DNA spots with the highest Cy5:Cy3 fluorescence ratios corresponded to a group of genes mapping within a 1 Mb interval centered near position 142.7 Mb on the X chromosome, the genomic location of HPRT. CONCLUSION: The results indicate that our physical mapping method based on radiation hybrids and array-CGH should significantly enhance the speed and efficiency of positional cloning in somatic cell genetics.

Animals↗

PubMed2003

Cytogenetic, spectral karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions, and MYC and MLL amplification.

Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML.

Acute Disease↗