Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chromosomal microarray analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 505 records · Page 28Linked to original sources
PubMed2005

[Molecular genetics in the diagnosis of bone and soft tissue tumours].

INTRODUCTION: Bone and soft tissue tumours are relatively rare; they make up about 1% of all new cancer cases, but around 10% among children and adolescents. MATERIAL AND METHODS: This review paper is based on searches in Medline and our own experience. RESULTS AND INTERPRETATION: There are a number of subgroups that require considerable experience. At the slightest suspicion of malignancy, no biopsy should be performed locally; the patient should be referred to a hospital with experience with this tumour type. Specific chromosomal aberrations have been described in several benign and malignant tumours; sarcomas may be divided into two subgroups based on cytogenetics, one with near-diploid karyotype and few chromosomal changes, but with specific translocations and one with complex karyotypes and multiple cytogenetic aberrations. Sarcomas should be karyotyped in order to identify chromosomal changes in general, whereas fluorescent in situ hybridisation and PCR are the most common methods for detecting the relevant, specific translocations. Genomic screening techniques, in particular microarray-based, global analyses of gene activities and copy numbers, will lead to smaller sets of informative gene assays that may be used in routine analysis. Gastrointestinal stromal tumour (GIST) is a tumour in the gastrointestinal tract where immunohistochemical analysis of the c-kit receptor and molecular diagnosis of mutations in the corresponding gene is important, as targeted therapy towards mutated versions of this receptor is available.

Adolescent↗
PubMed2004

Applications of genomic microarrays to explore human chromosome structure and function.

The combination of genomic microarrays with comparative genomic hybridization and with chromatin immunoprecipitation is providing an increasingly detailed view of the way in which the human genome is organized and functions and how disorganization and disfunction can lead to disease. These studies are enhanced by the flexibility of array technology, allowing resolutions from coverage of the whole genome using 200 kb cloned DNA inserts to detailed analysis using PCR products or oligonucleotides of 100 bp or less. In particular, the use of chromatin immunoprecipitation is providing new insights into chromosome structure and gene regulation and control through the analysis of protein--DNA interactions.

Chromatin Immunoprecipitation↗
PubMed2006

Genome-wide analysis of estrogen receptor binding sites.

The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation, particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Sample phenotype clusters in high-density oligonucleotide microarray data sets are revealed using Isomap, a nonlinear algorithm.

BACKGROUND: Life processes are determined by the organism's genetic profile and multiple environmental variables. However the interaction between these factors is inherently non-linear. Microarray data is one representation of the nonlinear interactions among genes and genes and environmental factors. Still most microarray studies use linear methods for the interpretation of nonlinear data. In this study, we apply Isomap, a nonlinear method of dimensionality reduction, to analyze three independent large Affymetrix high-density oligonucleotide microarray data sets. RESULTS: Isomap discovered low-dimensional structures embedded in the Affymetrix microarray data sets. These structures correspond to and help to interpret biological phenomena present in the data. This analysis provides examples of temporal, spatial, and functional processes revealed by the Isomap algorithm. In a spinal cord injury data set, Isomap discovers the three main modalities of the experiment--location and severity of the injury and the time elapsed after the injury. In a multiple tissue data set, Isomap discovers a low-dimensional structure that corresponds to anatomical locations of the source tissues. This model is capable of describing low- and high-resolution differences in the same model, such as kidney-vs.-brain and differences between the nuclei of the amygdala, respectively. In a high-throughput drug screening data set, Isomap discovers the monocytic and granulocytic differentiation of myeloid cells and maps several chemical compounds on the two-dimensional model. CONCLUSION: Visualization of Isomap models provides useful tools for exploratory analysis of microarray data sets. In most instances, Isomap models explain more of the variance present in the microarray data than PCA or MDS. Finally, Isomap is a promising new algorithm for class discovery and class prediction in high-density oligonucleotide data sets.

Algorithms↗
PubMed2005

Genomic profiling maps loss of heterozygosity and defines the timing and stage dependence of epigenetic and genetic events in Wilms' tumors.

To understand genetic and epigenetic pathways in Wilms' tumors, we carried out a genome scan for loss of heterozygosity (LOH) using Affymetrix 10K single nucleotide polymorphism (SNP) chips and supplemented the data with karyotype information. To score loss of imprinting (LOI) of the IGF2 gene, we assessed DNA methylation of the H19 5' differentially methylated region (DMR). Few chromosomal regions other than band 11p13 (WT1) were lost in Wilms' tumors from Denys-Drash and Wilms' tumor-aniridia syndromes, whereas sporadic Wilms' tumors showed LOH of several regions, most frequently 11p15 but also 1p, 4q, 7p, 11q, 14q, 16q, and 17p. LOI was common in the sporadic Wilms' tumors but absent in the syndromic cases. The SNP chips identified novel centers of LOH in the sporadic tumors, including a 2.4-Mb minimal region on chromosome 4q24-q25. Losses of chromosomes 1p, 14q, 16q, and 17p were more common in tumors presenting at an advanced stage; 11p15 LOH was seen at all stages, whereas LOI was associated with early-stage presentation. Wilms' tumors with LOI often completely lacked LOH in the genome-wide analysis, and in some tumors with concomitant 16q LOH and LOI, the loss of chromosome 16q was mosaic, whereas the H19 DMR methylation was complete. These findings confirm molecular differences between sporadic and syndromic Wilms' tumors, define regions of recurrent LOH, and indicate that gain of methylation at the H19 DMR is an early event in Wilms' tumorigenesis that is independent of chromosomal losses. The data further suggest a biological difference between sporadic Wilms' tumors with and without LOI.

Blotting, Northern↗
PubMed1999

Application of comparative genomic hybridization, spectral karyotyping, and microarray analysis in the identification of subtype-specific patterns of genomic changes in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) in children occurs predominantly as two major histologically defined subtypes called embryonal RMS (RMS-E) and the prognostically less favorable alveolar RMS (RMS-A). Comparative genomic hybridization (CGH) was performed on 21 RMS and identified consistent gains affecting chromosomes 2 (8/10), 5 (5/10), 6 (3/10), 7 (7/10), 8 (9/10), 11 (6/ 10), and 12 (5/10) in RMS-E. Losses/deletions involved chromosomes 19 (2/10) and chromosomes 4, 9, 10, 17, 21 (1/10 each). High copy number amplification, involving the 2p24 region (5/11) and less frequently, the 12q13-21 (2/11), 9p22 (1/11), and 17q22-25 (1/11) regions, was detected in RMS-A. Gene amplification at band 2p24 was present in 6/12 alveolar tumors, and in each case, MYCN was amplified, together with the distally placed DDX1 gene. For these patients there was a shorter disease free interval and a higher mortality than patients with tumors without amplification. Detailed spectral karyotype analysis (SKY) was performed on two RMS cell lines (one of each subtype) and identified a surprisingly high level of structural change. Gene expression studies with the Atlas Human Cancer Array (588 genes) showed that 153 genes generated a signal of similar intensity in both cell lines, and 45 genes appeared to have subtype-specific expression. The chromosomal location of differentially expressed genes was compared to the pattern of genomic alteration in RMS as determined by CGH in this study and the literature.

Chromosome Aberrations↗
PubMed2003

Hidden aberrations diagnosed by interphase fluorescence in situ hybridisation and spectral karyotyping in childhood acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is the most common oncologic disease in childhood, accounting for approximately 25% of all paediatric malignancies. Based on clinical risk criteria and modern laboratory investigations including immunophenotyping, cytogenetics and molecular genetics, patients can be divided into prognostic groups and assigned to risk-adjusted treatment protocols. The karyotype is an independent prognostic indicator and has for some aberrations that are associated with a poor outcome a direct impact on the choice of treatment. Cytogenetic analysis in ALL is often hampered by poor chromosome morphology, few malignant metaphases, undetectable chromosomal rearrangements due to regions of a similar size and banding pattern and sometimes only normal metaphases derived from normal cells are found after cell culture. Structural as well as numerical aberrations may therefore remain undetected using conventional G-banding. The application of modern molecular cytogenetic techniques including a broad set of fluorescence in situ hybridisation (FISH) methods and recent developments in comparative genomic hybridisation to DNA microarrays, together with molecular methods such as Southern blotting and RT-PCR has greatly improved the detection rate of genetic changes in ALL. This review emphasises the value of increasing the resolving power of the cytogenetic investigation by spectral karyotyping (SKY) and interphase FISH in identifying prognostically important and novel chromosomal rearrangements as a complement to conventional banding analysis. The results of investigations performed on cases with ALL have shown that interphase FISH is valuable and in many cases even mandatory for the detection of prognostically important genetic abnormalities and should therefore consistently be employed in the routine cytogenetic investigations in ALL. Likewise, SKY is a valuable tool for the cytogenetic analysis. Thus, the results of several different investigations described in this review revealed that SKY yielded additional information in 97/157 (62%) cases with chromosomal aberrations detected by G-banding, and in 10/66 (15%) cases with normal G-banding.

Blotting, Southern↗
PubMed2004

Detection and traceability of genetically modified organisms in the food production chain.

Both labelling and traceability of genetically modified organisms are current issues that are considered in trade and regulation. Currently, labelling of genetically modified foods containing detectable transgenic material is required by EU legislation. A proposed package of legislation would extend this labelling to foods without any traces of transgenics. These new legislations would also impose labelling and a traceability system based on documentation throughout the food and feed manufacture system. The regulatory issues of risk analysis and labelling are currently harmonised by Codex Alimentarius. The implementation and maintenance of the regulations necessitates sampling protocols and analytical methodologies that allow for accurate determination of the content of genetically modified organisms within a food and feed sample. Current methodologies for the analysis of genetically modified organisms are focused on either one of two targets, the transgenic DNA inserted- or the novel protein(s) expressed- in a genetically modified product. For most DNA-based detection methods, the polymerase chain reaction is employed. Items that need consideration in the use of DNA-based detection methods include the specificity, sensitivity, matrix effects, internal reference DNA, availability of external reference materials, hemizygosity versus homozygosity, extrachromosomal DNA, and international harmonisation. For most protein-based methods, enzyme-linked immunosorbent assays with antibodies binding the novel protein are employed. Consideration should be given to the selection of the antigen bound by the antibody, accuracy, validation, and matrix effects. Currently, validation of detection methods for analysis of genetically modified organisms is taking place. In addition, new methodologies are developed, including the use of microarrays, mass spectrometry, and surface plasmon resonance. Challenges for GMO detection include the detection of transgenic material in materials with varying chromosome numbers. The existing and proposed regulatory EU requirements for traceability of genetically modified products fit within a broader tendency towards traceability of foods in general and, commercially, towards products that can be distinguished from each other. Traceability systems document the history of a product and may serve the purpose of both marketing and health protection. In this framework, segregation and identity preservation systems allow for the separation of genetically modified and non-modified products from "farm to fork". Implementation of these systems comes with specific technical requirements for each particular step of the food processing chain. In addition, the feasibility of traceability systems depends on a number of factors, including unique identifiers for each genetically modified product, detection methods, permissible levels of contamination, and financial costs. In conclusion, progress has been achieved in the field of sampling, detection, and traceability of genetically modified products, while some issues remain to be solved. For success, much will depend on the threshold level for adventitious contamination set by legislation.

Animals↗
PubMed2002

A maximum entropy algorithm for rhythmic analysis of genome-wide expression patterns.

We introduce a maximum entropy-based analysis technique for extracting and characterizing rhythmic expression profiles from DNA microarray hybridization data. These patterns are clues to discovering genes implicated in cell-cycle, circadian, and other periodic biological processes. The algorithm, implemented in a program called ENRAGE (Entropy-based Rhythmic Analysis of Gene Expression), treats the task of estimating an expression profile's periodicity and phase as a simultaneous bicriterion optimization problem. Specifically, a frequency domain spectrum is reconstructed from a time-series of gene expression data, subject to two constraints: (a) the likelihood of the spectrum and (b) the Shannon entropy of the reconstructed spectrum. Unlike Fourier-based spectral analysis, maximum entropy spectral reconstruction is well suited to signals of the type generated in DNA microarray experiments. Our algorithm is optimal, running in linear time in the number of expression profiles. Moreover, an implementation of our algorithm runs an order of magnitude faster than previous methods. Finally, we demonstrate that ENRAGE is superior to other methods at identifying and characterizing periodic expression profiles on both synthetic and actual DNA microarray hybridization data.

Algorithms↗
PubMed2005

Mutations and deletions of the CBP gene in human lung cancer.

PURPOSE: Microarray-based comparative genomic hybridization analysis led us to detect a homozygous deletion at the cyclic AMP response element binding protein-binding protein (CBP) locus in a lung cancer cell line. Oncogenic roles of CBP had been suggested by functional and genetic studies; thus, involvement of CBP gene alterations in lung carcinogenesis was investigated by undertaking comprehensive analysis of genetic CBP alterations in human lung cancer. EXPERIMENTAL DESIGN: Fifty-nine cell lines and 95 surgical specimens of lung cancer were analyzed for mutations, homozygous and hemizygous deletions, and expression of the CBP gene. RESULTS: Homozygous CBP deletions, including two intragenic deletions, were detected in three (5.1%) lung cancer cell lines. CBP mutations, including missense, nonsense, and frame-shift mutations, were detected in six (10.2 %) cell lines and five (5.3%) surgical specimens of lung cancer. The wild-type CBP allele was retained in 9 of 11 cases with CBP mutations, and both the wild-type and mutant alleles were expressed in all the six cases with heterozygous CBP mutations examined. Three mutations with amino acid substitutions in the histone acetyltransferase domain caused significant reduction in transcription activation activity of CBP protein in vivo. CONCLUSIONS: A fraction of lung cancers carried mutations and/or deletions of the CBP gene, suggesting that genetic CBP alterations are involved in the genesis and/or progression of a subset of lung cancers.

Acetyltransferases↗
PubMed2004

Identification of DNA copy number changes in microdissected serous ovarian cancer tissue using a cDNA microarray platform.

We have established a method for using a cDNA array platform in combination with degenerate oligonucleotide primer polymerase chain reaction (DOP-PCR) and taramide signal amplification (TSA) to identify DNA copy number abnormalities (CNA) in cancer cell lines and cancer cells procured with laser-based microdissection. To determine the sensitivity and specificity for detecting single-copy gain and loss, receiver-operator curve analysis was performed on hybridization signal ratios generated from non-DOP and DOP amplified female and male DNA using a 10,816-element cDNA microarray. A cutoff value of 1.12 and 1.07 average signal ratio for X-chromosomal genes versus autosomal genes provided a sensitivity and specificity of 50 and 79%, respectively, for non-DOP amplified DNA and a sensitivity and specificity of 50 and 72%, respectively, for DOP amplified DNA. We used this approach to identify DNA copy number abnormalities in the ovarian cancer cell line OVCA633, which has previously been shown to have 12p amplification. Transcription profiling of OVCA633 was also performed. Two amplified and overexpressed genes located on 12p11, KRAS2 and LRMP, were identified; these were validated with quantitative real-time PCR. Subsequently, the same approach was used to identify CNAs and gene expression alterations in 11 microdissected serous ovarian adenocarcinoma cases. Validated data revealed amplification and overexpression of ERBB3 and FOS and deletion and underexpression of KRT6 and APXL in more than 50% of the tissue samples. These results show the feasibility of using the cDNA array platform to identify changes in DNA and mRNA copy number simultaneously in microdissected tumor tissues.

Adenocarcinoma↗
PubMed2003

Refined localization of dominant intermediate Charcot-Marie-Tooth neuropathy and exclusion of seven known candidate genes in the region.

Charcot-Marie-Tooth (CMT) neuropathy is one of the most common hereditary disorders of the human peripheral nervous system. The CMT syndrome includes weakness and atrophy of distal muscles, high arched feet (pes cavus), depressed or absent deep tendon reflexes, and mild sensory loss. Dominant intermediate CMT (DI-CMT) neuropathy is a form of CMT with intermediate median motor nerve conduction velocities. We previously localized the DI-CMT locus to a 16.8-cM region on chromosome 19p12-p13.2. Extended haplotype analysis and clinical assessment of additional family members and a report of a second family linked to this locus has enabled us to narrow the candidate region to a 6-cM interval flanked by D19S558 and D19S432. Selection of positional candidate genes for screening was performed on the basis of neural expression and microarray analysis of Schwann cell differentiation in vivo. Seven candidate genes have been investigated. These include six genes localized in the original linkage interval and one in the newly refined region. They are excluded as a cause for DI-CMT neuropathy.

Charcot-Marie-Tooth Disease↗
PubMed2006

Cluster analysis of networks generated through homology: automatic identification of important protein communities involved in cancer metastasis.

BACKGROUND: Protein-protein interactions have traditionally been studied on a small scale, using classical biochemical methods to investigate the proteins of interest. More recently large-scale methods, such as two-hybrid screens, have been utilised to survey extensive portions of genomes. Current high-throughput approaches have a relatively high rate of errors, whereas in-depth biochemical studies are too expensive and time-consuming to be practical for extensive studies. As a result, there are gaps in our knowledge of many key biological networks, for which computational approaches are particularly suitable. RESULTS: We constructed networks, or 'interactomes', of putative protein-protein interactions in the rat proteome--the rat being an organism extensively used for cancer studies. This was achieved by integrating experimental protein-protein interaction data from many species and translating this data into the reference frame of the rat. The putative rat protein interactions were given confidence scores based on their homology to proteins that have been experimentally observed to interact. The confidence score was furthermore weighted according to the extent of the experimental evidence, giving a higher weight to more frequently observed interactions. The scoring function was subsequently validated and networks constructed around key proteins, identified as being highly up- or down-regulated in rat cell lines of high metastatic potential. Using clustering methods on the networks, we have identified key protein communities involved in cancer metastasis. CONCLUSION: The protein network generation and subsequent network analysis used here, were shown to be useful for highlighting key proteins involved in metastasis. This approach, in conjunction with microarray expression data, can be extended to other species, thereby suggesting possible pathways around proteins of interest.

Algorithms↗
PubMed2005

Genomic profiling of myeloid sarcoma by array comparative genomic hybridization.

Myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells occurring in an extramedullary site. In this study, seven cases of MS [stomach (1), testis (1), skin (2), and lymph node (3)] and 3 synchronous and 1 follow-up bone marrow (BM) samples were studied for genomic abnormalities using array comparative genomic hybridization (array-CGH). Array-CGH construction used approximately 5,400 bacterial artificial chromosome clones from the RPCI-11 library, spanning the human genome. Data were analyzed using the DNAcopy software and custom heuristics. All MS cases had genomic abnormalities detected by array-CGH. Unbalanced genomic abnormalities in five MS cases were confirmed by conventional cytogenetics (CC) and/or fluorescence in situ hybridization (FISH); these abnormalities included loss of 4q32.1-q35.2, 6q16.1-q21, and 12p12.2-p13.2 and gain of 8q21.2-q24.3, 8, 11q21-q25, 13q21.32-q34, 19, and 21. Array-CGH was also invaluable in identifying possible deletions, partner translocations, and breakpoints that were questionable by CC. The remaining two MS cases had genomic aberrations detected by array-CGH, but were not studied further by CC/FISH. Chromosome 8 was most commonly abnormal (3/7 cases). Identical genomic abnormalities were demonstrated in MS and in synchronous BM in two cases. These results demonstrate that array-CGH is a powerful tool to screen MS tissue for unbalanced genomic abnormalities, allowing identification of chromosome abnormalities when concurrent BM is nonanalyzable or nonleukemic.

Adult↗
PubMed2006

Identification of large-scale human-specific copy number differences by inter-species array comparative genomic hybridization.

Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee, bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla. The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications (SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity.

Animals↗
PubMed2007

High-resolution analysis of allelic imbalance in neuroblastoma cell lines by single nucleotide polymorphism arrays.

Genomic copy number changes are detectable in many malignancies, including neuroblastoma, using techniques such as comparative genomic hybridization (CGH), microsatellite analysis, conventional karyotyping, and fluorescence in situ hybridization (FISH). We report the use of 10K single nucleotide polymorphism (SNP) microarrays to detect copy number changes and allelic imbalance in six neuroblastoma cell lines (IMR32, SHEP, NBL-S, SJNB-1, LS, and SKNBE2c). SNP data were generated using the GeneChip DNA Analysis and GeneChip chromosome copy number software (Affymetrix). SNP arrays confirmed the presence of all previously reported cytogenetic abnormalities in the cell lines, including chromosome 1p deletion, MYCN amplification, gain of 17q and 11q, and 14q deletions. In addition, the SNP arrays revealed several chromosome gains and losses not detected by CGH or karyotyping; these included gain of 8q21.1 approximately 24.3 and gain of chromosome 12 in IMR-32 cells; loss at 4p15.3 approximately 16.1 and loss at 16p12.3 approximately 13.2, 11q loss with loss of heterozygosity (LOH) at 11q14.3 approximately 23.3 in SJNB-1 cells; and loss at 8p21.2 approximately 23.3 and 9p21.3 approximately 22.1 with corresponding LOH in SHEP cells. The SNP arrays refined the mapping of the 2p amplicons in LS, BE2c, and IMR-32 cell lines, the 12q amplicon in LS cells, and also identified an 11q13 amplicon in LS cells. There was good concordance among SNP arrays, CGH, and karyotyping. SNP array analysis is a powerful tool for the detection of allelic imbalance in neuroblastoma and also allows identification of LOH without changes in copy number (uniparental disomy).

Allelic Imbalance↗
PubMed2006

Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements.

Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods. We applied 5C to analyze a 400-kb region containing the human beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by detection of several previously identified looping interactions in the beta-globin locus. We also identified a new looping interaction in K562 cells between the beta-globin Locus Control Region and the gamma-beta-globin intergenic region. Interestingly, this region has been implicated in the control of developmental globin gene switching. 5C should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure.

Base Sequence↗
PubMed2006

High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines.

Tumours develop from clonally expanded population of cells harbouring aberrations of oncogenes and tumour suppressor genes. In this study, metaphase and array comparative genomic hybridization showed good correlation of aberration profiles in lung adenocarcinoma cell lines from patients with different tobacco exposure. Recurrent DNA gains were found at chromosomes 1, 7, 8, 17, 20, and deletions at 1, 3, 8, 9, 10, 12, 17, 18, 19. Candidate tumour loci and encompassed genes at 7p21 (AGR2), 8q21(TPD52), 20q13 (ZNF217, WFDC2, EEF1A2) and 10p15 (KLF6) were analyzed by dual colour FISH for genomic changes and quantitative PCR for expression changes. Results indicated that EEF1A2 and KLF6 were strong candidates of oncogene and tumour suppressor genes, respectively. This study illustrates, a practical strategy for identifying candidate cancer genes from microarray data.

Adenocarcinoma↗