Faculty Opinions recommendation of Replication stress induces genome-wide copy number changes in human cells that resemble polymorphic and pathogenic variants.

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC.Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed.Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

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Comparative Genomic Analyses of Primary Effusion Lymphoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-0824-cgaope ◽

2000 ◽

Vol 124 (6) ◽

pp. 824-826

Author(s):

B. P. Mullaney ◽

V. L. Ng ◽

B. G. Herndier ◽

M. S. McGrath ◽

M. G. Pallavicini

Keyword(s):

Copy Number ◽

Primary Effusion Lymphoma ◽

Immune Surveillance ◽

Comparative Genomic ◽

Limited Information ◽

Human Herpes Virus 8 ◽

Regulatory Pathways ◽

Genome Wide ◽

Unique Markers ◽

Copy Number Changes

Abstract Background.—A rare subset of human immunodeficiency virus (HIV) lymphomas, known as primary effusion lymphomas (PELs), are high-grade tumors carrying human herpes virus 8. Mechanisms postulated to contribute to lymphomagenesis include impaired immune surveillance, alterations in hemopoietic regulatory pathways due to expressed viral genes, and acquisition of genomic alterations in regions of the genome that contain regulatory genes. In PEL, limited information exists about the nature of genome-wide aberrations in these rare lymphomas. Methods.—We used comparative genomic hybridization to detect regions of sequence gain and loss throughout the genome of 8 PEL cases. Regions of DNA sequence loss or gain were confirmed using forward and reverse hybridization and t-statistic analyses. Results.—Genomic aberrations were identified in 6 of 8 cases, including recurrent gain of sequence in chromosomes 12 [ish enh (12q22;12q23, 12q12;12q23)] in 3 of 8 cases and X [ish enh (X, Xp)] in 2 of 8 cases. Conclusions.—DNA copy number changes occurred in a majority of PEL cases and are consistent with changes observed in other HIV lymphomas. These observations suggest that common genetic events may occur in HIV-associated lymphoid malignancies, but they probably do not contribute to the unique markers and morphology of PEL. Although individual genetic loci have been evaluated previously in a few PEL cases, to our knowledge this study represents the first reported genome-wide scan of copy number changes in these rare HIV-associated tumors.

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POS-02.12: Analysis of genome-wide copy number changes in bladder cancers using array-based comparative genomic hybridization

Urology ◽

10.1016/j.urology.2007.06.752 ◽

2007 ◽

Vol 70 (3) ◽

pp. 236

Author(s):

S. Eguchi ◽

Y. Yamamoto ◽

Y. Chochi ◽

T. Furuya ◽

A. Oga ◽

...

Keyword(s):

Comparative Genomic Hybridization ◽

Copy Number ◽

Comparative Genomic ◽

Genomic Hybridization ◽

Genome Wide ◽

Copy Number Changes

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Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays

Haematologica ◽

10.3324/haematol.12603 ◽

2008 ◽

Vol 93 (7) ◽

pp. 994-1000 ◽

Cited By ~ 30

Author(s):

L. Wang ◽

C. Fidler ◽

N. Nadig ◽

A. Giagounidis ◽

M. G. Della Porta ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Myelodysplastic Syndrome ◽

Loss Of Heterozygosity ◽

Copy Number ◽

High Density ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Genome Wide Analysis ◽

Genome Wide ◽

Copy Number Changes

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Genome-Wide Analysis of Subependymomas Shows Underlying Chromosomal Copy Number Changes Involving Chromosomes 6, 7, 8 and 14 in a Proportion of Cases

Brain Pathology ◽

10.1111/j.1750-3639.2008.00148.x ◽

2008 ◽

Vol 0 (0) ◽

pp. 080407141616718-??? ◽

Cited By ~ 5

Author(s):

Kathreena M. Kurian ◽

David T.W. Jones ◽

Faye Marsden ◽

Sam W.S. Openshaw ◽

Danita M. Pearson ◽

...

Keyword(s):

Copy Number ◽

Genome Wide Analysis ◽

Genome Wide ◽

Chromosomal Copy Number ◽

Chromosomal Copy ◽

Copy Number Changes

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Canvas: versatile and scalable detection of copy number variants

10.1101/036194 ◽

2016 ◽

Author(s):

Eric Roller ◽

Sergii Ivakhno ◽

Steve Lee ◽

Thomas Royce ◽

Stephen Tanner

Keyword(s):

Copy Number ◽

Large Scale ◽

Copy Number Variants ◽

Variant Calling ◽

Experimental Designs ◽

Genome Wide ◽

Whole Exome ◽

Sequencing Studies ◽

Copy Number Changes ◽

Robust Variant

Motivation: Increased throughput and diverse experimental designs of large-scale sequencing studies necessi-tate versatile, scalable and robust variant calling tools. In particular, identification of copy number changes re-mains a challenging task due to their complexity, susceptibility to sequencing biases, variation in coverage data and dependence on genome-wide sample properties, such as tumor polyploidy or polyclonality in cancer samples. Results: We have developed a new tool, Canvas, for identification of copy number changes from diverse se-quencing experiments including whole-genome matched tumor-normal and single-sample normal re-sequencing, as well as whole-exome matched and unmatched tumor-normal studies. In addition to variant calling, Canvas infers genome-wide parameters such as cancer ploidy, purity and heterogeneity. It provides fast and simple to execute workflows that can scale to thousands of samples and can be easily incorporated into existing variant calling pipelines. Availability: Canvas is distributed under an open source license and can be downloaded from https://github.com/Illumina/canvas.

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Copy number evolution in simple and complex tandem repeats across the C57BL/6 and C57BL/10 inbred mouse lines

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab184 ◽

2021 ◽

Author(s):

Jullien M Flynn ◽

Emily J Brown ◽

Andrew G Clark

Keyword(s):

Copy Number ◽

Copy Number Change ◽

Tandem Repeats ◽

Inbred Mouse ◽

Rate Of Change ◽

Rates Of Change ◽

Centromeric Repeat ◽

Genome Wide ◽

Copy Number Changes ◽

Simple Repeats

Abstract Simple sequence tandem repeats are among the most rapidly evolving compartments of the genome. Some repeat expansions are associated with mammalian disease or meiotic segregation distortion, yet the rates of copy number change across generations are not well known. Here, we use 14 distinct sub-lineages of the C57BL/6 and C57BL/10 inbred mouse strains, which have been evolving independently over about 300 generations, to estimate the rates of copy number changes in genome-wide tandem repeats. Rates of change varied across repeats and across lines. Notably, CAG, whose expansions in coding regions are associated with many neurological and genetic disorders, was highly stable in copy number, likely indicating stabilizing selection. Rates of change were positively correlated with copy number, but the direction and magnitude of changes varied across lines. Some mouse lines experienced consistent losses or gains across most simple repeats, but this did not correlate with copy number changes in complex repeats. Rates of copy number change were similar between simple repeats and the more abundant complex repeats after normalization by copy number. Finally, the Y-specific centromeric repeat had a 4-fold higher rate of change than the homologous centromeric repeat on other chromosomes. Structural differences in satellite complexity, or restriction to the Y chromosome and elevated mutation rates of the male germline, may explain the higher rate of change. Overall, our work underscores the mutational fluidity of long tandem arrays of repeats, and the correlations and constraints between genome-wide tandem repeats which suggest that turnover is not a completely neutral process.

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Genomic Tumour Profiling with High-Density Oligonucleotide SNP Array in Sézary Syndrome.

Blood ◽

10.1182/blood.v108.11.2289.2289 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2289-2289

Author(s):

Giandomenico Russo ◽

Maria Grazia Narducci ◽

Mauro Helmer Citterich ◽

Maria Cristina Picchio ◽

Cristina Critofoletti ◽

...

Keyword(s):

Copy Number ◽

Dna Analysis ◽

Snp Array ◽

Significant Loss ◽

High Density ◽

Chromosome 17 ◽

Genome Wide ◽

Snp Mapping ◽

Mapping Array ◽

Copy Number Changes

Abstract Sézary Syndrome (SS) is a rare and aggressive form of Cutaneous T-Cell Lymphoma (CTCL) characterised by a distinct metastatic pattern mainly involving blood and skin and whose etiology and molecular pathogenesis are still unclear. Conventional cytogenetics studies have shown that most SS patients have chromosome aberrations; however allelotyping studies and genome-wide surveys for chromosome imbalances in this tumour are still very limited (Mao X. et al. 2003 Genes Chromosome Cancer 36:250–260). High-density single nucleotide polymorphism (SNP) arrays allow high-resolution and genome-wide detection of both loss of heterozygosity (LOH) and copy number (CN) abnormality. Therefore we used Affymetrix 10K SNP mapping array containing 11,560 tiled SNPs to investigate genomic aberrations of 13 individuals affected by SS. Genotype calls and signal information were obtained using GeneChip Operating Software (GCOS 1.4) and GeneChip DNA Analysis Software (GTYPE4.0). SNP calls were exported to be analysed with DNA-chip Analyser (dChip v1.3+) genotyping software which allows the simultaneous measurement of DNA copy number changes and LOH events (Zhao X. et al. 2004 Cancer Res. 64:3060–71; Lin M et al. 2004 Bioinformatics 20:1233–40). Our findings indicate that chromosomes 17p, 10/10q and 9 are most frequently affected by LOH events, while gains of CN were observed more often for chromosome 17q and 8/8q. Among our patients almost all individuals showing loss of the 17p arm have also gain of the 17q, suggesting the presence of the isochromosome 17q, a frequently reported abnormality in SS. In addition to this, we characterised the chromosome LOH pattern identifying seven regions of significant loss shared by multiple tumours. Sample clustering based on significant LOH regions identified two groups of patients: one of them consists of 4 patients with a lower rate of chromosomal losses while the other contains 9 patients mainly characterised by the co-occurrence of LOH at chromosome 17 and chromosome 10. The frequency and pattern of chromosomal changes in our group of 13 SS patients are in substantial agreement with previously described results using more conventional techniques, demonstrating the feasibility of the 10K SNP mapping array system to assess allelic imbalance in this tumour. The genome-wide approach and SNP high density allowed the identification of a larger number of LOH regions, including, however, those already described (chromosome 9p, 10q and 17p). Even though no significant statistical association can be observed due to the low number of cases available, we observed a lower overall survival in the group of 9 patients showing simultaneous LOH events at chromosome 17 and 10.

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