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Results for “Relative copy number variation”

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PubMed1994

Amplification of the ancient murine Lx family of long interspersed repeated DNA occurred during the murine radiation.

We identified and characterized the relics of an ancient rodent L1 family, referred to as Lx, which was extensively amplified at the time of the murine radiation about 12 million years ago, and which we showed was ancestral to the modern L1 families in rat and mouse. Here we have extended our analysis of the Lx amplification by examining more murine and nonmurine species for Lx sequences using both blot hybridization and the polymerase chain reaction for a total of 36 species. In addition we have determined the relative copy number and sequence divergence, or age, of Lx elements in representative murine genera. Our results show that while Lx sequences are confined to murine genera, the extent of the amplification was different in the different murine lineages, indicating that the amplification of Lx did not precede, but was coincident with, the murine radiation. The implications of our findings for the evolutionary dynamics of L1 families and the utility of ancestral amplification events for systematics are discussed.

Animals↗

PubMed2001

Identification and characterization of variable-number tandem repeats in the Yersinia pestis genome.

Yersinia pestis, the infamous plague-causing pathogen, appears to have emerged in relatively recent history. Evidence of this fact comes from several studies that document a lack of nucleotide diversity in the Y. pestis genome. In contrast, we report that variable-number tandem repeat (VNTR) sequences are common in the Y. pestis genome and occur frequently in gene coding regions. Larger tandem repeat arrays, most useful for phylogenetic analysis, are present at an average of 2.18 arrays per 10 kbp and are distributed evenly throughout the genome and the two virulence plasmids, pCD1 and pMT1. We examined allelic diversity at 42 chromosomal VNTR loci in 24 selected isolates (12 globally distributed and 12 from Siskiyou County, Calif.). Vast differences in diversity were observed among the 42 VNTR loci, ranging from 2 to 11 alleles. We found that the maximum copy number of repeats in an array was highly correlated with diversity (R = 0.86). VNTR-based phylogenetic analysis of the 24 strains successfully grouped isolates from biovar orientalis and most of the antiqua and mediaevalis strains. Hence, multiple-locus VNTR analysis (MLVA) appears capable of both distinguishing closely related strains and successfully classifying more distant relationships. Harnessing the power of MLVA to establish standardized databases will enable researchers to better understand plague ecology and evolution around the world.

Animals↗

PubMed2026

Identification and characterization of ectopic chromosomal amplifications in acute myeloid leukemia cell limes using high-throughput chromosome conformation capture screening.

Despite advanced molecular diagnostics, improving outcomes for refractory acute myeloid leukemia (AML) remains challenging. Although many cancer-related genes are identified, their molecular mechanisms are not fully elucidated. Amplification is a mechanism of cancer-associated gene activation, and ectopic gene amplification may have particularly high pathological significance. However, research on ectopically amplified cancer-associated genes in leukemia remains limited. Here, we evaluated the usefulness of high-throughput chromosomal conformation capture (Hi-C) as a screening method for ectopic gene amplification and assessed whether ectopic amplification of cancer-associated genes may represent a general phenomenon in AML. We screened the U-937 and NB-4 cell lines using in situ Hi-C. Regions appearing as "high-intensity bands" in Hi-C contact maps were identified and validated using fluorescence in situ hybridization (FISH). Additionally, copy number variation analysis was performed using whole-genome sequencing (WGS) to extract cancer-associated genes with ectopic amplification. In the U-937, three genomic regions showing "high-intensity bands" were identified and confirmed as ectopic amplifications-including PDCD1LG2 (PD-L2), CD274 (PD-L1), and JAK2; that is, four copies were detected by WGS, and amplification signals were observed by FISH. In the NB-4, four such regions were detected, including MYC and KRAS, with expression level of 498 transcripts per million (TPM) and 34 TPM, respectively. Copy number variation analysis further identified multiple cancer-associated genes with ectopic amplification. Overall, these findings demonstrate the presence of ectopic amplification of cancer-associated genes in AML cell lines and support the usefulness of Hi-C as a screening method for detecting such genomic alterations.

Acute myeloid leukemia↗

PubMed2006

Mapping tumor-suppressor genes with multipoint statistics from copy-number-variation data.

Array-based comparative genomic hybridization (arrayCGH) is a microarray-based comparative genomic hybridization technique that has been used to compare tumor genomes with normal genomes, thus providing rapid genomic assays of tumor genomes in terms of copy-number variations of those chromosomal segments that have been gained or lost. When properly interpreted, these assays are likely to shed important light on genes and mechanisms involved in the initiation and progression of cancer. Specifically, chromosomal segments, deleted in one or both copies of the diploid genomes of a group of patients with cancer, point to locations of tumor-suppressor genes (TSGs) implicated in the cancer. In this study, we focused on automatic methods for reliable detection of such genes and their locations, and we devised an efficient statistical algorithm to map TSGs, using a novel multipoint statistical score function. The proposed algorithm estimates the location of TSGs by analyzing segmental deletions (hemi- or homozygous) in the genomes of patients with cancer and the spatial relation of the deleted segments to any specific genomic interval. The algorithm assigns, to an interval of consecutive probes, a multipoint score that parsimoniously captures the underlying biology. It also computes a P value for every putative TSG by using concepts from the theory of scan statistics. Furthermore, it can identify smaller sets of predictive probes that can be used as biomarkers for diagnosis and therapeutics. We validated our method using different simulated artificial data sets and one real data set, and we report encouraging results. We discuss how, with suitable modifications to the underlying statistical model, this algorithm can be applied generally to a wider class of problems (e.g., detection of oncogenes).

Gene Deletion↗

PubMed2005

Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3.

We have defined unexpectedly extensive copy number variation at the human anti-microbial alpha-defensin genes DEFA1 and DEFA3, encoding human neutrophil peptides HNP-1, HNP-2 and HNP-3. There was variation in both number and position of DEFA1/DEFA3 genes in arrays of 19 kb tandem repeats on 8p23.1, so that the DEFA1 and DEFA3 genes appear to be interchangeable variant cassettes within tandem gene arrays. For this reason, the official symbol for this locus has been revised to DEFA1A3. The total number of gene copies per diploid genome varied between four and 11 in a sample of 111 control individuals from the UK, with approximately 10% (11/111) of people lacking DEFA3 completely. DEFA1 appeared to be at high copy number in all great apes studied; at one variable site in the repeat unit, both variants have persisted in humans, chimpanzees and gorillas since their divergence. Analysis of expression levels in human white blood cells showed a clear correlation between the relative proportions of DEFA1:DEFA3 mRNA and corresponding gene numbers. However, there was no relationship between total (DEFA1+DEFA3) mRNA levels and total gene copy number, suggesting the superimposed influence of trans-acting factors. The persistence of DEFA1 at high copy number in other apes suggests an alternative model for the early stages of the evolution of novel genes by duplication and divergence. Duplicated genes present in variant tandem arrays may have greater potential than simple duplications for the combinatorial creation of new functions by recombination and gene conversion, while still preserving pre-existing functions on the same haplotype.

Blotting, Southern↗

PubMed1985

Transition stages of molecular drive in multiple-copy DNA families in Drosophila.

Multigene and non-genic DNA families are in a state of turnover and hence are continually being replaced throughout a population by new variant repeats. To quantify such molecular processes, in the absence of selection, it is necessary to find and compare stages of transistion during the homogenization of at least two non-genic families evolving in parallel in a closely related group of species. Detailed sequence analysis of patterns of variation, at each nucleotide position considered independently, amongst repeats of two tandem DNA families from seven related Drosophila species, reveals all stages of transition during the spread of randomly produced variant repeats. Variant repeats are found at different stages of homogenization and fixation in a population, irrespective of the loci, chromosomes or individuals from which they were cloned. Differences between the families in the relatively small number of variants at each transition stage and the greater number of fully homogenized and fixed variants between species of greater divergence indicate that the process of spread (molecular drive) is rapid relative to the mutation rate and occurs at seemingly different constant rates for each family. Occasional gene conversions, in addition to unequal exchanges, have contributed to family turnover. The significance of these results to the evolution of functional multigene families and divergence and conservation of sequences is discussed.

Journal Article↗

PubMed1984

Evolving sea urchin histone genes--nucleotide polymorphisms in the H4 gene and spacers of Strongylocentrotus purpuratus.

We present a comparison of spacer and coding sequences of histone gene repeats from four Strongylocentrotus purpuratus individuals. Sequences of two previously cloned units (pCO2 and pSp2) were compared with three new histone gene clones, two of them from a single individual. Within a 1.7-kb region, 59 polymorphic sites were found in spacers, in mRNA nontranslated stretches, and at silent sites in codons of the H4 gene. The permitted silent-site changes were as frequent as in any other region studied. The most abundant polymorphisms were single-base substitutions. The ratio of transitions : transversions : single-base-pair insertions/deletions was 3:2:2. A number of larger insertions/deletions were found, as well as differences in the length of (CTA)n and (CT)n runs. Two of the five cloned repeats contained an insertion of a 195-bp element that is also present at many other sites in the genomes of every S. purpuratus individual studied. Pairwise comparisons of the different clones indicate that the variation is not uniformly divergent, but ranges from a difference of 0.34% to 3.0% of all nucleotide sites. A parsimonious tree of ancestry constructed from the pairwise comparisons indicates that recombination between the most distantly related repeats has not occurred in the 1-2 million years necessary for accumulation of the variation. The level of sequence variation found within the S. purpuratus population, for both tandemly repeated and single-copy genes, is 25%-50% of that found between S. purpuratus and S. drobachiensis.

Alleles↗

PubMed1991

Human T-cell receptor V alpha gene polymorphism.

Polymorphism in the germline repertoire of T-cell receptor (TCR) variable alpha and beta (V alpha and V beta) genes could alter the relative abilities of individuals in a population to respond to particular antigens. Variation in the number of germline V alpha and V beta gene segments has been reported in wild mice and in different inbred mouse strains. A previous study of the human V beta gene germline repertoire failed to reveal a similar degree of polymorphism in the numbers of V beta gene segments. We have now carried out a survey of 10 different V alpha gene segment subfamilies containing approximately 23 V alpha gene segments in a panel of 120 unrelated individuals by hybridization and failed to find any evidence for V alpha repertoire polymorphism. To determine if significant germline polymorphism does occur in humans at the level of individual V gene segments, we determined the nucleotide sequences of eight copies of the V alpha 21 gene segment derived from seven unrelated individuals. Polymorphic differences between these sequences defined three different alleles. One of these alleles contains a frameshift mutation which would cause premature termination of the protein product. The presence of this null allele among the eight sequences determined suggests that functionally relevant germline polymorphism of human TCR V gene segments may occur by mechanisms other than gene duplication or deletion.

Amino Acid Sequence↗

PubMed2002

Genetic instability in cancer tissues analyzed by random amplified polymorphic DNA PCR.

OBJECTIVE: To detect DNA and chromosomes instabilities during the progression of tumors and screen new molecular markers coupled to putative or unknown oncogenes and/or tumor suppressor genes. METHODS: Five kinds of tumors, in a total of 128 specimens, were analyzed by random amplified polymorphic DNA (RAPD) PCR. Bands representing instabilities were recovered, purified, and cloned, labeled as probes for Southern and Northern blot analysis and DNA sequencing. RESULTS: Sample 5 and 3 of the gastric cancer tissues showed the highest genomic changes and the average detectability in five cancers was up to at least 40% (42.2% - 49.4%). There were significant differences in the ability of each primer to detect genomic instability, which ranged from 27% (primer 8) to 68% (primer 2). Band B is a single copy fragment, and was found to be an allelic loss in gastric and colon cancers. It is a novel sequence and was registered in GenBank with Accession Number AF151005. Further analysis revealed that it might be part of a cis-regulatory element of a new tumor suppressor gene, containing a promoter of cis-action "CACA" box, an enhancer of "GATA" family and a start codon. CONCLUSIONS: It was impossible or difficult to get great achievements for cancer treatments with the procedure of gene therapy only to one oncogene or one tumor suppressor gene because the extensive DNA variations occurred during the progression of tumor. RAPD assay connected with other techniques was a good tool for the detection of genomic instabilities and direct screening of some new molecular markers related to tumor suppressor genes or oncogenes.

Base Sequence↗

PubMed2002

Insertion polymorphism of retrotransposable elements in populations of the insular, endemic species Drosophila madeirensis.

The insertion site numbers of the retrotransposable elements (TE) 412, gypsy and bilbo were determined in individuals of five distinct natural populations of the endemic species Drosophila madeirensis from the island of Madeira. The TE distributions were compared to those of the paleartic, widespread and phylogenetically closely related species, D. subobscura. In situ hybridization and Southern blots showed that in D. madeirensis the number of insertion sites ranged between 10 and 15, three and six, and 35 and 42 for elements 412, gypsy and bilbo, respectively. The corresponding values for D. subobscura were similar. Two of these elements, 412 and gypsy, had very few insertions in the heterochromatin, unlike bilbo, which displayed a high heterochromatic insertion number. The Southern band polymorphism was very high, leading to within-population variation of 97.2%, whatever the population and the TE concerned. Using the polymorphic TE insertion sites as markers to analyse population structure by AMOVA, adapted for RAPD (Randomly Amplified Polymorphic DNA) data, we found small but significant genetic differences between the populations on Madeira. This slight differentiation, coupled with similar copy numbers for each TE between populations, suggests that the D. madeirensis species consists of a single, only slightly subdivided population. These data also show that insular populations and endemic species of Drosophila can have as many copies of TEs as more widespread species.

Animals↗

PubMed1996

Age-dependent silencing of globin transgenes in the mouse.

Variegation of transgene expression, a heterocellular or mosaic pattern of expression seen in all mice in a given transgenic line, is a frequently observed but unexplained phenomenon. We have encountered variegation with globin transgenes; when lacZ expression is driven by globin control elements a proportion of erythrocytes express beta-galactosidase (beta-gal), while the remaining erythrocytes express none. The percentage of expressing cells is constant within each line (at any particular developmental stage), but varies between lines. Such variation may account for much of the line-to-line variability which has been reported in the expression of a transgene construct. We have now extended these observations by studying expression of several globin/lacZ transgenes with increasing age. Expression of beta-gal is variegated in all lines in adult mice, including those made with a beta-globin promoter and locus control region driving lacZ. The extent of variegation differs widely between lines, but in all lines there is a marked decline in the number of erythrocytes expressing beta-gal with increasing age. Progression of silencing continues long past the point at which globin switching is complete, suggesting that it is not related to this process. We observe that age-dependent silencing is most severe in high copy number animals. Increasing variegation of transgene expression with ageing of mice is likely to complicate interpretation of the developmental regulation of transgenes. We speculate that it reflects a general mechanism of epigenetic regulation.

Aging↗

PubMed2004

An RT-PCR-based strategy to estimate full-length CYP2D6 mRNA copy number.

The goal of this study is to develop an analytical tool to assess cytochrome P450 2D6 (CYP2D6) levels in the form of full-length transcripts. CYP2D6 RNA in test samples was evaluated by co-amplification with an internal RNA control in a reverse-transcribed polymerase chain reaction (RT-PCR). The internal CYP2D6 RNA control was constructed by internally deleting 474 bp of CYP2D6 RNA, allowing simultaneous amplification of the test RNA together with the internal control RNA in a single RT-PCR reaction. With sequential dilution of test RNA, the CYP2D6 mRNA transcript levels in test samples were estimated. The full-length RT-PCR strategy allowed semiquantitative assessments of CYP2D6 RNA transcripts with a sensitivity limit of 500 copies for CYP2D6 RNA transcripts, 2500 copies/microg total human liver RNA, and 10% intraday coefficient of variation (CV). In a method validation study, the CYP2D6 activity appeared to relate more closely to full-length CYP2D6 mRNA concentration than a short-sequence of CYP2D6 RNA estimated with a real-time quantitative RT-PCR assay. We have developed an efficient semiquantitative assay and demonstrated its suitability for estimating full-length CYP2D6 mRNA transcripts in cells and tissues.

Cytochrome P-450 CYP2D6↗

PubMed1993

Immunocytochemical localization of c-erbB-2 protein in transitional cell carcinoma of the urinary bladder.

The level of expression and cellular localization of the c-erbB-2 gene product in transitional cell carcinoma of the urinary tract is controversial. Analysis of the c-erbB-2 gene structure and comparison of its expression in the same cells by Southern, Northern and immunoblotting, and by immunocytochemistry minimize the errors of interpretation inherent in one technique. Such a 'correlative study' has been performed on tumours from 82 patients. c-erbB-2 gene amplification was detected in 14 per cent of initial tumours and was associated with grade (P < 0.001). Raised levels of mRNA were seen in those tumours with increased gene copy number and in 13 per cent of the remainder. Immunoblotting detected the expected 185 kD immunoreactive protein and a 155 kD protein associated with high gene copy number. Immunocytochemistry localized c-erbB-2 immunoreactivity to the cell membrane and cytoplasm, and the latter predominated. Four antibodies to c-erbB-2 (AB-3, 21N, pAb 1, and NCL CB11) were compared on contiguous sections of the same tumour and showed the same pattern of immunoreactivity. Similarly, analyses carried out in three independent laboratories identified the same cellular localization. Membrane and cytoplasmic immunoreactivity was demonstrated in all tumours with gene amplification or increased mRNA levels and in 40 per cent of the remaining tumours. We showed that immunocytochemistry requires careful standardization of techniques and quantitation between different groups. However, despite variations in the intensity of immunoreactivity, the total number of positive cells remained constant. Therefore quantitation must be based on the number of positive cells and, ideally, their immunoreactive content relative to normal and positive tissue controls.

Biomarkers, Tumor↗

PubMed2002

Variable levels of chromosomal instability and mitotic spindle checkpoint defects in breast cancer.

Cytogenetic analyses have revealed that many aneuploid breast cancers have cell-to-cell variations of chromosome copy numbers, suggesting that these neoplasms have instability of chromosome numbers. To directly test for possible chromosomal instability in this disease, we used fluorescent in situ hybridization to monitor copy numbers of multiple chromosomes in cultures of replicating breast cancer-derived cell lines and nonmalignant breast epithelial cells. While most (7 of 9) breast cancer cell lines tested are highly unstable with regard to chromosome copy numbers, others (2 of 9 cell lines) have a moderate level of instability that is higher than the "background" level of normal mammary epithelial cells and MCF-10A cells, but significantly less than that seen in the highly unstable breast cancer cell lines. To evaluate the potential role of a defective mitotic spindle checkpoint as a cause of this chromosomal instability, we used flow cytometry to monitor the response of cells to nocodazole-induced mitotic spindle damage. All cell lines with high levels of chromosomal instability have defective mitotic spindle checkpoints, whereas the cell lines with moderate levels of chromosomal instability (and the stable normal mammary cells and MCF10A cells) arrest in G(2) when challenged with nocodazole. Notably, the extent of mitotic spindle checkpoint deficiency and chromosome numerical instability in these cells is unrelated to the presence or absence of p53 mutations. Our results provide direct evidence for chromosomal instability in breast cancer and show that this instability occurs at variable levels among cells from different cancers, perhaps reflecting different functional classes of chromosomal instability. High levels of chromosomal instability are likely related to defective mitotic checkpoints but not to p53 mutations.

Breast Neoplasms↗

PubMed2006

Proteomic and genomic characterization of Kunitz trypsin inhibitors in wild and cultivated soybean genotypes.

In this study, we investigated protein and genetic profiles of Kunitz trypsin inhibitors (KTIs) in seeds of 16 different soybean genotypes that included four groups consisting of wild soybean (Glycine soja), the cultivated soybean (G. max) ancestors of modern N. American soybean cultivars (old), modern N. American soybean (elite), and Asian cultivated soybean landraces that were the immediate results of domestication from the wild soybean. Proteins were well separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and stained protein cut from a 2D-PAGE indicated that KTI exists as multiple isoforms (spots) in soybean. Protein spots of KTI were identified and characterized using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Although overall distribution patterns of the KTI protein spots appeared similar, the number and intensity of the protein spots between wild and cultivated genotypes varied. Three KTI peptides were identified in three of the wild genotypes, PI 393551, PI 407027 and PI 407282, in which KTI3 peptide showed highest intensity. The remaining wild genotype, PI 366120, showed four protein spots. In contrast, the ancestors, modern and Asian landrace genotypes showed only two protein spots corresponding to KTI. On the basis of DNA blot analysis, there is one copy of the KTI3 gene in all 16 genotypes. Polymorphism was detected in one of the wild genotypes (PI 366120) both in proteomic and genomic analyses. Our data suggest that the major variation of protein profiles were between wild and cultivated soybean genotypes rather than among genotypes in the same group. Genetic variation of KTI1, KTI2 and KTI3-related genes were detected within and between groups.

Base Sequence↗

PubMed2004

An analysis of the neural representation of birdsong memory.

Songbirds, such as zebra finches, learn their song from a tutor early in life. Forebrain nuclei in the "song system" are important for the acquisition and production of song. Brain regions [including the caudomedial part of the neostriatum (NCM) and of the hyperstriatum ventrale (CMHV)] outside the song system show increased neuronal activation, measured as expression of immediate early genes (IEGs), when zebra finch males are exposed to song. IEG expression in the NCM in response to tutor song is significantly positively correlated with the strength of song learning (i.e., the number of elements copied). Here, we exposed three groups of adult zebra finch males to tutor song, to their own song, or to novel conspecific song. The two control groups were included to examine an alternative explanation of our previous results in terms of variation in predisposed levels of attentiveness. Expression of Zenk, the protein product of the IEG ZENK, was measured in the NCM, CMHV, and hippocampus. There were no significant differences in overall Zenk expression between the three experimental groups. However, there was a significant positive correlation between Zenk expression in the NCM (but not in the other two regions) and strength of song learning in the males that were exposed to the tutor song. There was no such correlation in the other two groups. These results suggest that experience-related neuronal activation is specific to the tutor song and thus unlikely to be a result of differences in attention.

Analysis of Variance↗

PubMed1998

Chromosomal organization of amplified chromosome 12 sequences in mesenchymal tumors detected by fluorescence in situ hybridization.

The chromosomal organization of amplified chromosome 12 sequences was studied with fluorescence in situ hybridization in six mesenchymal tumors: two osteosarcomas, one lipoma, two liposarcomas, and one fibrosarcoma. All except the fibrosarcoma contained ring and/or giant marker chromosomes. Amplification of chromosome 12 sequences, demonstrated with whole-chromosome paint in all cases, was confined to ring and giant marker chromosomes in four tumors. In one of the osteosarcomas and in the fibrosarcoma, amplified sequences were added to chromosome 12 and to chromosomes 10, 12, 18, and the Y chromosome, respectively. Hybridizations with single-copy probes demonstrated considerable inter- and intracellular variation in the arrangement of chromosome 12 sequences in ring and marker chromosomes. Amplification of 12q13-15 sequences, predominantly from the HMGIC-MDM2 region, was detected in all cases, but the two osteosarcomas also contained amplification of 12p material. This finding, combined with results from previous studies, indicates that 12p amplification is a feature distinguishing osteosarcomas from adipose tissue tumors. A novel finding was the presence of positive signals for chromosome 12 alpha-satellite sequences in ring and marker chromosomes in four cases. Rod chromosomes carrying amplified material, in particular those that were relatively stable, frequently exhibited chromosome 12 negative terminal segments; two of these, present in two separate cases, were shown by C-banding to contain constitutive heterochromatin. The significant intercellular heterogeneity in the number and structure of rings and giant markers in a subset of mesenchymal tumors could be explained by continuous recombination through breakage-fusion-bridge cycles. If so, this process will continue until broken ends become stabilized, for example by acquisition of telomeric segments from other chromosomes.

Adolescent↗

PubMed1987

Cell-specific ribosomal DNA spacer variability in human urothelial carcinoma cultures.

Length variation of a ribosomal DNA "spacer" region in four chromosomally characterized transitional cell carcinoma cultures was analyzed by restriction endonuclease cleavage and Southern blotting. Cell lines with relative karyotypic conservation, such as UM-UC-2 (modal chromosome number 48, four marker chromosomes) demonstrate little change in the genetically regulated pattern of rDNA spacer length polymorphisms (7.6, 6.7 and 6.0 kilobases) which may be found in normal cells. Cell lines with more aberrant karyotypes, such as UM-UC-3 (modal chromosome number 86, 12 marker chromosomes) and UM-UC-4 (modal number 51, ten marker chromosomes) show fewer ribosomal DNA length variants (7.6, 6.7 kilobases for the former, 7.6 kilobases for the latter), consistent with relaxed constraints on the drive for ribosomal gene homogeneity through inter and intrachromosomal exchange. Uncharacterized rDNA length variants of low copy number were observed in cell lines with many marker chromosomes. Analysis of repetitive DNA structure provides an additional criterion for tumor diagnosis and staging, and a characterized series of tumor cell lines may provide a useful system for understanding repetitive DNA evolution.

Carcinoma, Transitional Cell↗