scholarly journals Cluster Analysis of Comparative Genomic Hybridization (CGH) Data Using Self-Organizing Maps: Application to Prostate Carcinomas

2001 ◽  
Vol 23 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Torsten Mattfeldt ◽  
Hubertus Wolter ◽  
Ralf Kemmerling ◽  
Hans‐Werner Gottfried ◽  
Hans A. Kestler
Keyword(s):  
Cluster Analysis ◽  
Comparative Genomic Hybridization ◽  
Genetic Material ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Self Organizing Maps ◽  
Data Set ◽  
A Genome ◽  
Self Organizing

Comparative genomic hybridization (CGH) is a modern genetic method which enables a genome‐wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that region. Usually it is not possible to evaluate all 46 chromosomes of a metaphase, therefore several (up to 20 or more) metaphases are analyzed per individual, and expressed as average. Mostly one does not study one individual alone but groups of 20–30 individuals. Therefore, large amounts of data quickly accumulate which must be put into a logical order. In this paper we present the application of a self‐organizing map (Genecluster) as a tool for cluster analysis of data from pT2N0 prostate cancer cases studied by CGH. Self‐organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule, i.e., in our examples it gets the CGH data as only information (no clinical data). We studied a group of 40 recent cases without follow‐up, an older group of 20 cases with follow‐up, and the data set obtained by pooling both groups. In all groups good clusterings were found in the sense that clinically similar cases were placed into the same clusters on the basis of the genetic information only. The data indicate that losses on chromosome arms 6q, 8p and 13q are all frequent in pT2N0 prostatic cancer, but the loss on 8p has probably the largest prognostic importance.

scholarly journals Chromosomal Regions in Prostatic Carcinomas Studied by Comparative Genomic Hybridization, Hierarchical Cluster Analysis and Self-Organizing Feature Maps

2002 ◽  
Vol 24 (4-5) ◽  
pp. 167-179 ◽  
Author(s):  
Torsten Mattfeldt ◽  
Hubertus Wolter ◽  
Danilo Trijic ◽  
Hans‐Werner Gottfried ◽  
Hans A. Kestler
Keyword(s):  
Cluster Analysis ◽  
Comparative Genomic Hybridization ◽  
Hierarchical Cluster Analysis ◽  
Hierarchical Cluster ◽  
Data Matrix ◽  
Comparative Genomic ◽  
Feature Maps ◽  
Genomic Hybridization ◽  
A Genome ◽  
Self Organizing

Comparative genomic hybridization (CGH) is an established genetic method which enables a genome‐wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that place. Therefore, large amounts of data quickly accumulate which must be put into a logical order. Cluster analysis can be used to assign individual cases (samples) to different clusters of cases, which are similar and where each cluster may be related to a different tumour biology. Another approach consists in a clustering of chromosomal regions by rewriting the original data matrix, where the cases are written as rows and the chromosomal regions as columns, in a transposed form. In this paper we applied hierarchical cluster analysis as well as two implementations of self‐organizing feature maps as classical and neuronal tools for cluster analysis of CGH data from prostatic carcinomas to such transposed data sets. Self‐organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule. We studied a group of 48 cases of incidental carcinomas, a tumour category which has not been evaluated by CGH before. In addition we studied a group of 50 cases of pT2N0‐tumours and a group of 20 pT3N0‐carcinomas. The results show in all case groups three clusters of chromosomal regions, which are (i) normal or minimally affected by losses and gains, (ii) regions with many losses and few gains and (iii) regions with many gains and few losses. Moreover, for the pT2N0‐ and pT3N0‐groups, it could be shown that the regions 6q, 8p and 13q lay all on the same cluster (associated with losses), and that the regions 9q and 20q belonged to the same cluster (associated with gains). For the incidental cancers such clear correlations could not be demonstrated.

Array Comparative Genomic Hybridization: Impact in the Assessment of Plasma Cell Myeloma Genetic Profile and Prognosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4965-4965
Author(s):  
Annette Leon ◽  
Deborah Sevilla ◽  
Joseph M Marino ◽  
Kenneth D Moreno ◽  
Rev Obrera ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Plasma Cell ◽  
Array Comparative Genomic Hybridization ◽  
Genetic Material ◽  
Chromosome Complement ◽  
Comparative Genomic ◽  
Genetic Profile ◽  
Telomeric Region ◽  
Plasma Cell Myeloma ◽  
Genomic Hybridization

Abstract Abstract 4965 Identification of specific chromosomal alterations in plasma cell myeloma (PCM) is essential for the prognosis and treatment of this disease. Although cytogenetic chromosome and fluorescence in situ hybridization (FISH) analyses are techniques currently used for this purpose, incorporation of array comparative genomic hybridization (aCGH) analysis as described in this study, demonstrates the insufficient power of traditional techniques in characterizing the complex and heterogeneous genetic profile of this group of hematological malignancies. In our cohort, aCGH study of 500 diagnosed PCM patients identified clinically significant genomic alterations in 56% of cases compared to 22% and 32% by chromosome and FISH analyses, respectively. Important findings by aCGH include the presence of hyperdiploid chromosome complement (15 > 9 > 5 > 19 > 11 > 3 > 7 > 21 > 6 > 18 >14) in 35% of cases which is associated with a favorable prognosis, as well as adverse prognostic markers such as hypodiploid chromosome complement (13 > Y >14 > 22> 10 >16 >8), gain of genetic material in chromosome 1q (CKS1B, PDZK1, ANP32E) and losses in chromosomes 1p (CDKN2C, FAM46C), 6q (PRDM1), 12p (ETV6, CDKN1B), and 17p (TP53) observed in 25% of patients. Recurrent alterations identified in 9% of cases only by aCGH include extra copies of genes which could be potentially poor prognostic indicators such as IRF4 (6p25. 3, transactivates MYC oncogene), IL-6 (7p15. 3, growth factor), BRAF (7q34, regulating the MAP kinase/ERKs signaling pathway), CYLC2 (9q31. 1, active cyclin in cell cycle progression from G1 to S phase), and genes located in the telomeric region of chromosome Xq. The results obtained in this study demonstrate the superior resolution and detection rate of aCGH technology in understanding the genetic heterogeneity of PCM as well as the importance of incorporating this methodology into current algorithms for the diagnosis and prognosis of plasma cell disorders. Disclosures: No relevant conflicts of interest to declare.

Comparative Genomic Hybridization

2001 ◽  
Vol 125 (1) ◽  
pp. 81-84
Author(s):  
Irene J. Barrett ◽  
Brenda L. Lomax ◽  
Tatiana Loukianova ◽  
Steven S. Tang ◽  
Valia S. Lestou ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Hybridization Analysis ◽  
Comparative Genomic ◽  
Amniotic Fluid Cell ◽  
Comparative Genomic Hybridization Analysis ◽  
Clinical Tool ◽  
Genomic Hybridization ◽  
Maternal Cell ◽  
Fetal Tissues ◽  
A Genome

Abstract Objective.—To demonstrate the effectiveness of comparative genomic hybridization (CGH) for analysis of reproductive pathology specimens in clinical cytogenetics laboratories. Design.—A total of 856 CGH analyses were performed on various placental and fetal tissues derived from 368 specimens of spontaneous abortions and on placentas from 219 pregnancies with live-born infants. The live-born infants were clinically evaluated as normally developed, with either a normal birth weight or with intrauterine growth restriction; some live-born infants had an abnormal prenatal triple screen with normal cytogenetic results on amniotic fluid cell cultures. Results.—Comparative genomic hybridization analysis was successfully performed on 856 samples from spontaneously aborted specimens and term placentas. Failure of analysis occurred in 1.6% of samples and was due to an insufficient amount of tissue for DNA extraction. Comparative genomic hybridization identified aneuploidy in 53% of spontaneous abortion samples and 3.1% of term placentas. Conclusions.—Comparative genomic hybridization analysis is a useful clinical tool for detection of aneuploidy in placental and fetal tissues. It provides a genome-wide screen while eliminating tissue culture failures, culture artifacts, and maternal cell contamination. We present practical guidelines for interpreting CGH profiles derived from human reproductive specimens.

Gene expression analysis of chromosomal regions with gain or loss of genetic material detected by comparative genomic hybridization

2004 ◽  
Vol 41 (4) ◽  
pp. 353-365 ◽  
Author(s):  
Bárbara Meléndez ◽  
Ramón Díaz-Uriarte ◽  
Marta Cuadros ◽  
Ángel Martínez-Ramírez ◽  
José Fernández-Piqueras ◽  
...  
Keyword(s):  
Gene Expression ◽  
Comparative Genomic Hybridization ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Genetic Material ◽  
Comparative Genomic ◽  
Genomic Hybridization

scholarly journals Expanded Multilocus Sequence Typing and Comparative Genomic Hybridization of Campylobacter coli Isolates from Multiple Hosts

2010 ◽  
Vol 76 (6) ◽  
pp. 1913-1925 ◽  
Author(s):  
Ping Lang ◽  
Tristan Lefebure ◽  
Wei Wang ◽  
Paulina Pavinski Bitar ◽  
Richard J. Meinersmann ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Host Species ◽  
Multilocus Sequence Typing ◽  
Evolutionary History ◽  
Comparative Genomic ◽  
Campylobacter Coli ◽  
Genomic Hybridization ◽  
Data Set ◽  
History Of ◽  
Microarray Comparative Genomic Hybridization

ABSTRACT The purpose of this work was to evaluate the evolutionary history of Campylobacter coli isolates derived from multiple host sources and to use microarray comparative genomic hybridization to assess whether there are particular genes comprising the dispensable portion of the genome that are more commonly associated with certain host species. Genotyping and ClonalFrame analyses of an expanded 16-gene multilocus sequence typing (MLST) data set involving 85 isolates from 4 different hosts species tentatively supported the development of C. coli host-preferred groups and suggested that recombination has played various roles in their diversification; however, geography could not be excluded as a contributing factor underlying the history of some of the groups. Population genetic analyses of the C. coli pubMLST database by use of STRUCTURE suggested that isolates from swine form a relatively homogeneous genetic group, that chicken and human isolates show considerable genetic overlap, that isolates from ducks and wild birds have similarity with environmental water samples and that turkey isolates have a connection with human infection similar to that observed for chickens. Analysis of molecular variance (AMOVA) was performed on these same data and suggested that host species was a significant factor in explaining genetic variation and that macrogeography (North America, Europe, and the United Kingdom) was not. The microarray comparative genomic hybridization data suggested that there were combinations of genes more commonly associated with isolates derived from particular hosts and, combined with the results on evolutionary history, suggest that this is due to a combination of common ancestry in some cases and lateral gene transfer in others.

scholarly journals Characterization of the Genome Composition of Bartonella koehlerae by Microarray Comparative Genomic Hybridization Profiling

2005 ◽  
Vol 187 (17) ◽  
pp. 6155-6165 ◽  
Author(s):  
Hillevi L. Lindroos ◽  
Alex Mira ◽  
Dirk Repsilber ◽  
Olga Vinnere ◽  
Kristina Näslund ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Bartonella Henselae ◽  
Sequence Divergence ◽  
Genomic Islands ◽  
Vector System ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Bartonella Quintana ◽  
A Genome ◽  
Wide Range

ABSTRACT Bartonella henselae is present in a wide range of wild and domestic feline hosts and causes cat-scratch disease and bacillary angiomatosis in humans. We have estimated here the gene content of Bartonella koehlerae, a novel species isolated from cats that was recently identified as an agent of human endocarditis. The investigation was accomplished by comparative genomic hybridization (CGH) to a microarray constructed from the sequenced 1.93-Mb genome of B. henselae. Control hybridizations of labeled DNA from the human pathogen Bartonella quintana with a reduced genome of 1.58 Mb were performed to evaluate the accuracy of the array for genes with known levels of sequence divergence. Genome size estimates of B. koehlerae by pulsed-field gel electrophoresis matched that calculated by the CGH, indicating a genome of 1.7 to 1.8 Mb with few unique genes. As in B. quintana, sequences in the prophage and the genomic islands were reported absent in B. koehlerae. In addition, sequence variability was recorded in the chromosome II-like region, where B. koehlerae showed an intermediate retention pattern of both coding and noncoding sequences. Although most of the genes missing in B. koehlerae are also absent from B. quintana, its phylogenetic placement near B. henselae suggests independent deletion events, indicating that host specificity is not solely attributed to genes in the genomic islands. Rather, the results underscore the instability of the genomic islands even within bacterial populations adapted to the same host-vector system, as in the case of B. henselae and B. koehlerae.

Array Comparative Genomic Hybridization: A Better Alternative for Genomic Profiling and Prognosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4572-4572
Author(s):  
Annette Leon ◽  
Deborah Sevilla ◽  
Joseph M Marino ◽  
Kenneth D Moreno ◽  
Rev Obrera ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Comparative Genomic Hybridization ◽  
Peripheral Blood ◽  
Array Comparative Genomic Hybridization ◽  
Genetic Material ◽  
Lymphocytic Leukemia ◽  
Comparative Genomic ◽  
Small Lymphocytic Lymphoma ◽  
Genomic Hybridization

Abstract Abstract 4572 Traditional cytogenetic techniques such as chromosome analysis and fluorescence in situ hybridization (FISH) have provided valuable genetic information in the evaluation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). However, many genomic abnormalities remain undetected due to the limitations intrinsic to these techniques. We designed, validated, and clinically applied a combined targeted-whole genome custom oligonucleotide microarray for the evaluation of hematological malignancies. Incorporation of array comparative genomic hybridization (aCGH) analysis has enabled us to identify previously undetected copy number changes with an increased resolution and sensitivity and more precisely determine genomic breakpoints and gene content with diagnostic and prognostic relevance in CLL/SLL. A cohort of 300 patients diagnosed with CLL/SLL was studied using concurrent cytogenetics, FISH and aCGH analyses on either peripheral blood or bone marrow aspirate samples. Array CGH identified clinically significant genomic alterations in 75% of the cases compared to 57% and 47% by cytogenetics and FISH analyses, respectively. There were no statistically significant differences detected between peripheral blood and bone marrow samples. Recurrent alterations such as deletions in chromosomes 11q (ATM, adverse prognosis), 13q (RB1, DLEU1, 2, and 7, MIR15A and 16–1, favorable prognosis in general), 17p (TP53, adverse prognosis) and gain of one copy of the entire chromosome 12 (ETV6, KLRK1, CD27, KRAS, MDM2, HIP1R, KITLG, intermediate prognosis) were identified in 55% of cases by aCGH. Of these cases, chromosome and/or FISH analyses did not detect these abnormalities in 42% and 27% of cases respectively. In addition, aCGH study more fully characterized the interstitial deletion in chromosome 13q recently suggested to have different outcomes based on size and gene content. Important findings exclusively by aCGH analysis in 7% of cases include loss of genetic material in chromosomes 3p (KAT2B, FHIT, clonal evolution), 6q (MAP3K7, PRDM1, AIM1, TNFAIP3, intermediate prognosis), 8p (TNFRSF10D, disease progression), 9q (JAK2, MLLT3, CDKN2A and B, DAPK1) and gain of genetic material in chromosome 2p (ACP1, MYCN, ALK, REL, BCL11A) associated with unmutated IGHV status, advanced disease stage and adverse prognosis. The results obtained in this study demonstrate the superior resolution and detection rate of aCGH technology as well as the importance of incorporating this methodology into current algorithms for the diagnosis and prognosis of CLL/SLL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Array-comparative genomic hybridization in sporadic benign pheochromocytomas

2009 ◽  
Vol 16 (2) ◽  
pp. 505-513 ◽  
Author(s):  
Francien H van Nederveen ◽  
Esther Korpershoek ◽  
Ronald J deLeeuw ◽  
Albert A Verhofstad ◽  
Jacques W Lenders ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
High Frequency ◽  
Chromosomal Abnormalities ◽  
Neurofibromatosis Type ◽  
The Other ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Von Hippel Lindau ◽  
A Genome ◽  
High Resolution Analysis

Pheochromocytomas (PCC) are catecholamine-producing tumors arising from the adrenal medulla that occur either sporadically or in the context of hereditary cancer syndromes, such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease (VHL), neurofibromatosis type 1, and the PCC-paraganglioma syndrome. Conventional comparative genomic hybridization studies have shown loss of 1p and 3q in the majority of sporadic and MEN2-related PCC, and 3p and 11p loss in VHL-related PCC. The development of a submegabase tiling resolution array enabled us to perform a genome-wide high-resolution analysis of 36 sporadic benign PCC. The results show that there are two distinct patterns of abnormalities in these sporadic PCC, one consisting of loss of 1p with or without concomitant 3q loss in 20/36 cases (56%), the other characterized by loss of 3p with or without concomitant 11p loss in 11/36 (31%). In addition, we found loss of chromosome 22q at high frequency (35%), as well as the novel finding of high frequency chromosome 21q loss (21%). We conclude that there appear to be two subgroups of benign sporadic PCC, one of which has a pattern of chromosomal abnormalities that is comparable with PCC from patients with MEN2 and the other that is comparable with the PCC that arise in patients with VHL disease. In addition, genes on 21q and 22q might play a more important role in PCC pathogenesis than had been assumed thus far.

Multiple genetic aberrations including evidence of chromosome 11q13 rearrangement detected in pituitary adenomas by comparative genomic hybridization

1999 ◽  
Vol 90 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Andrew K. Metzger ◽  
Gayatry Mohapatra ◽  
Yuriko A. Minn ◽  
Andrew W. Bollen ◽  
Kathleen Lamborn ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Comparative Genomic Hybridization ◽  
Pituitary Adenomas ◽  
Genetic Material ◽  
Comparative Genomic ◽  
Chromosome 11 ◽  
Genomic Hybridization ◽  
Genetic Aberrations ◽  
Content Type ◽  
Fine Print

Object. This study was conducted to determine whether comparative genomic hybridization (CGH) is a more sensitive method for detecting genetic aberrations than other tests currently in use.Methods. The authors used CGH to examine 40 primary and 13 recurrent adenomas obtained from 52 patients for loss and gain of genetic material. Copy number aberrations (CNAs) were detected in 25 (48%) of the 52 patients studied. The chromosomes affected were, in order of decreasing frequency, 11, 7, X, 1, 8, 13, 5, 14, 2, 6, 9, 10, 12, 3, 18, 21, 4, 16, 15, 19, 22, and Y. Endocrinologically active adenomas were more likely to contain (p = 0.009) and had a greater number (p = 0.003) of CNAs. Of 26 adenomas with CNAs, 18 showed multiple aberrations involving entire chromosomes or chromosome arms. The most frequent CNA involving a chromosome subregion, which was present in four (8%) of 53 adenomas, was the loss of all chromosome 11 material except for a preserved common segment containing 11q13. Immunoperoxidase staining did not detect cyclin D1 expression in those four cases, making cyclin D1 an unlikely target of this rearrangement.Conclusions. These findings indicate that genetic abnormalities are present in pituitary adenomas at a higher rate than previously reported, are associated with endocrinological activity, and often involve several chromosomes. Rearrangement at 11q13 may inactivate a tumor suppressor gene or activate an oncogene that is important in the initiation or progression of sporadic pituitary adenomas.

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