Confirmation of the copy number of chromosome 1 in interphase nuclei from paraffin sections of breast tumours by fluorescencein situ hybridization

1995 ◽  
Vol 3 (7) ◽  
pp. 410-416 ◽  
Author(s):  
Marie-Louise Loupart ◽  
Rosemary Walker ◽  
William Brammar ◽  
Jennifer Varley
Keyword(s):  
Copy Number ◽  
Chromosome 1 ◽  
Fluorescencein Situ Hybridization ◽  
Paraffin Sections ◽  
Interphase Nuclei ◽  
Breast Tumours

scholarly journals From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 502
Author(s):  
Georgiana Gug ◽  
Caius Solovan
Keyword(s):  
Mycosis Fungoides ◽  
Copy Number ◽  
Snp Array ◽  
Chromosome 1 ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
Large Plaque ◽  
Inflammatory Dermatosis ◽  
Fresh Frozen ◽  
Dna Copy Number Alterations

Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential role in the genesis of cancer out of genes expression dysregulation. Objectives: Due to the heterogeneity of MF and LPP and the scarcity of the cases, there are an exceedingly small number of studies that have identified molecular changes in these pathologies. We aim to identify and compare DNA copy number alterations and gene expression changes between MF and LPP to highlight the similarities and the differences between these pathologies. Materials and Methods: The patients were prospectively selected from University Clinic of Dermatology and Venereology Timișoara, Romania. From fresh frozen skin biopsies, we extracted DNA using single nucleotide polymorphism (SNP) data. The use of SNP array for copy number profiling is a promising approach for genome-wide analysis. Results: After reviewing each group, we observed that the histograms generated for chromosome 1–22 were remarkably similar and had a lot of CNAs in common, but also significant differences were seen. Conclusions: This study took a step forward in finding out the differences and similarities between MF and LPP, for a more specific and implicitly correct approach of the case. The similarity between these two pathologies in terms of CNAs is striking, emphasizing once again the difficulty of approaching and differentiating them.

Somatic pairing of chromosome 1 centromeres in interphase nuclei of human cerebellum

1989 ◽  
Vol 83 (3) ◽  
pp. 231-234 ◽  
Author(s):  
E. P. J. Arnoldus ◽  
A. C. B. Peters ◽  
G. T. A. M. Bots ◽  
A. K. Raap ◽  
M. van der Ploeg
Keyword(s):  
Chromosome 1 ◽  
Interphase Nuclei ◽  
Human Cerebellum ◽  
Somatic Pairing

scholarly journals Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eva Kriegova ◽  
Regina Fillerova ◽  
Jiri Minarik ◽  
Jakub Savara ◽  
Jirina Manakova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
High Risk ◽  
Copy Number ◽  
Optical Mapping ◽  
Chromosome 1 ◽  
Gene Copy ◽  
Whole Genome ◽  
Myeloma Cells ◽  
Genomic Architecture

AbstractExtramedullary disease (EMM) represents a rare, aggressive and mostly resistant phenotype of multiple myeloma (MM). EMM is frequently associated with high-risk cytogenetics, but their complex genomic architecture is largely unexplored. We used whole-genome optical mapping (Saphyr, Bionano Genomics) to analyse the genomic architecture of CD138+ cells isolated from bone-marrow aspirates from an unselected cohort of newly diagnosed patients with EMM (n = 4) and intramedullary MM (n = 7). Large intrachromosomal rearrangements (> 5 Mbp) within chromosome 1 were detected in all EMM samples. These rearrangements, predominantly deletions with/without inversions, encompassed hundreds of genes and led to changes in the gene copy number on large regions of chromosome 1. Compared with intramedullary MM, EMM was characterised by more deletions (size range of 500 bp–50 kbp) and fewer interchromosomal translocations, and two EMM samples had copy number loss in the 17p13 region. Widespread genomic heterogeneity and novel aberrations in the high-risk IGH/IGK/IGL, 8q24 and 13q14 regions were detected in individual patients but were not specific to EMM/MM. Our pilot study revealed an association of chromosome 1 abnormalities in bone marrow myeloma cells with extramedullary progression. Optical mapping showed the potential for refining the complex genomic architecture in MM and its phenotypes.

scholarly journals LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci

2021 ◽  
Author(s):  
Luca Comai ◽  
Kirk R Amundson ◽  
Benny Ordonez ◽  
Xin Zhao ◽  
Guilherme Tomaz Braz ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Large Scale ◽  
Chromosomal Translocations ◽  
Chromosome 1 ◽  
Structural Variations ◽  
Painting Probes ◽  
Two Populations

Large scale structural variations, such as chromosomal translocations, can have profound effects on fitness and phenotype, but are difficult to identify and characterize. Here, we describe a simple and effective method aimed at identifying translocations using only the dosage of sequence reads mapped on the reference genome. We binned reads on genomic segments sized according to sequencing coverage and identified instances when copy number segregated in populations. For each dosage-polymorphic 1Mb bin, we tested linkage disequilibrium with other variable bins. In nine potato (Solanum tuberosum) dihaploid families translocations affecting pericentromeric regions were common and in two cases were due to genomic misassembly. In two populations, we found evidence for translocation affecting euchromatic arms. In cv. PI 310467, a non-reciprocal translocation between chromosome 7 and 8 resulted in a 5-3 copy number change affecting several Mb at the respective chromosome tips. In cv. Alca Tarma the terminal arm of chromosome 4 translocated to the tip of chromosome 1. Using oligonucleotide-based fluorescent in situ hybridization painting probes (oligo-FISH), we tested and confirmed the predicted arrangement in PI 310467. In 192 natural accessions of Arabidopsis thaliana, dosage haplotypes tended to vary continuously and resulted in higher noise, but we identified pericentromeric LD suggesting the effect of repeats. This method should be useful in species where translocations are suspected because it tests linkage without the need for genotyping.

scholarly journals Multiomic Mapping of Copy Number and Structural Variation on Chromosome 1 (Chr1) Highlights Multiple Recurrent Disease Drivers

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 721-721
Author(s):  
Patrick Blaney ◽  
Eileen M Boyle ◽  
Yubao Wang ◽  
Hussein Ghamlouch ◽  
Jinyoung Choi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Board Of Directors ◽  
Cell Lines ◽  
Chromatin Structure ◽  
Copy Number ◽  
Research Funding ◽  
Chromosome 1 ◽  
Structural Variants ◽  
Advisory Committees

Abstract Introduction Copy number abnormalities (CNA) and structural variants (SV) are crucial to driving cancer progression and in multiple myeloma (MM). Chr1 CNA are seen in up to 40% of cases and associate with poor prognosis. Variants include deletions, gains, translocations and complex SV events such as chromothripsis (CT), chromoplexy (CP) and templated insertions (TI) which result in aberrant transcriptional patterns. Abnormal expression of genes on chr1 lead to the adverse clinical outcome and studies focussed on 1p12, 1p32.3 and 1q12-21 identified potential causal genes including TENT5C, CDKN2C, CKS1B, PDZK1, BCL9, ANP32E, ILF2, ADAR, MDM2 and MCL1 but none fully explain the clinical behavior. To address this deficiency and to relate chromatin structure to gene deregulation we present a multiomic bioinformatic analysis of SV, CNA, mutation and expression changes in relation to the chromatin structure of chr1. Methods We analysed data derived from 1,154 CoMMpass trial patients. We analyzed 972 NDMM patients with whole exome for mutations, and 752 whole genomes for copy number, translocations, complex rearrangements such as CP, CT and TI as previously described. Using GISTIC 2.0, we identified hotspots of CNA. This information was then analyzed in conjunction to the RNA-seq data derived from 643 patients to determine the aberrant transcriptional landscape of chr1. Using HiC data derived from U266 MM cell line, we associated these changes with TAD structures, A/B compartments, and histone marks along chr1, to gene expression changes, and recurrent SV. Using the cell line dependency map for CRISPR knockdown of the gene set on chr1 derived from 20 MM cell lines we related cell viability to chr1 copy number status. Results We identified 7 hotspots of deletion, 9 of gain, 3 of CT and 2 of templated-insertion across chr1. We mapped these regions to epigenetic plots and show that gained regions are hypomethylated compared to the rest of chr1 (Wilcoxon, p=0.0002). Overall 69% of gain(1q) and 45% of the non-gained hotspots were in A compartments (χ 2=11, p=0.0009) and had an overall higher compartment score (p=0.01).The recurrent regions of loss on 1p confirm the clinical relevance of this region. The critical importance of TENT5C, CDKN2C and RPL5 is identified by the impact of deletion, mutation and the rearrangement of superenhancers. Further this convergence of multiple oncogeneic mechanisms to a single locus points to a number of novel candidate drivers including FUB1 and NTRK1.We provide important new information on 1q21.1-1q25.2 encompassing 145-180Mb a transcriptionally dense region containing 6 GISTIC 2.0 hotspots of gain (G2-G7). The hotspots occur within TAD structures that correlate upregulation of known drivers listed above and also identified novel potential upregulated drivers including POU2F1, a transcription factor, CREG1, an adenovirus E1A protein that both activates and represses gene expression promoting proliferation and inhibiting differentiation (G6) and BTG2 a G1/S transition regulator (G8). These data for copy number gain provides strong evidence for the prognostic relevance of of multiple drivers within deregulated TADs rather than single candidate genes. It also highlights the importance of the chromatin structure of Chr1 in the generation of these events.Using dependency map CRISPR data we identified 320 essential genes for at least one cell line (>1). A common set of 31 genes were identified including 3 proteasome subunits (PSMA5, PSMB2, PSMB4), three regulators of ubiquitin-protein transferase activity (RPL5, RPL11, CDC20), splicing (SF3B4, SF3A3, SFPQ, RNPC3, SRNPE, PRPF38A, PRPF38B) and DTL. A common dependency for 1q+ or 1p- was not identified but a number of dependencies were identified in more than one cell line including UQCRH, SLCA1, CLSPN in 1p- cell lines and IPO9, PPIAL4G, and MRPS2 in 1q+. Conclusion We present an elegant anatomic map of chr1 at the genetic and epigenetic levels providing an unprecedented level of resolution for the relationships of structural variants to epigenetic, expression and mutation status. The analysis highlights the importance of active chromatin in gene deregulation by SV and CNA where the importance of multiple gene deregulation within TAD structures is critical to MM pathogenesis. The implications are that we could improve prognostic assignment and identify new targets for therapy by further characterizing these relationships. Figure 1 Figure 1. Disclosures Braunstein: Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Davies: Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Constellation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Recurrent Additional Genetic Aberrations and a Novel Mechanism of CBFB-MYH11-Rearrangement in AML M4eo Are Detected Using High-Resolution Genome-Wide Single Nucleotide Polymorphisms (SNPs) Microarrays

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3115-3115
Author(s):  
Alexander Kohlmann ◽  
Sonja Rauhut ◽  
Frank Dicker ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosome Banding ◽  
Fusion Gene ◽  
Physical Map ◽  
Snp Array ◽  
Chromosome 8 ◽  
Chromosome 1 ◽  
Banding Analysis ◽  
Chromosome Banding Analysis ◽  
7Q Deletion

Abstract Leukemia specific fusion genes such as CBFB-MYH11 play a major role in the pathogenesis of distinct AML entities. However, additional genetic aberrations seem necessary for the development of full blown leukemia. This study was performed to decipher CBFB-MYH11 rearrangements and their accompanying genetic lesions at the molecular level. Therefore, Affymetrix SNP Array 6.0 analyses, featuring >1.8 million markers for genetic variation (>906,600 SNPs and >946,000 probes for the detection of copy number variations), were performed in 35 newly diagnosed AML with inv(16) (p13q22) or t(16;16)(p13;q22) and CBFB-MYH11-rearrangement. First, as a proof of principle, additional gains and losses of chromosomal material as observed by cytogenetics were also detected by the SNP technology. This included gains of whole chromosome 8 (n=7) and 22 (n=8). In addition, a partial trisomy 13 and a partial trisomy 6 resulting from an unbalanced translocation were confirmed. In two cases a 7q deletion was observed by chromosome banding analysis. One of these was missed by SNP array as the 7q deletion occurred in a subclone only (11% of cells with 7q deletion as determined by interphase FISH). However, SNP array analyses detected loss of 7q in two additional cases which was missed by cytogenetics. Based on SNP array data the commonly deleted region was identified to range from 7q36.1 to 7q36.3 (size: 8.5 MB; physical map position 147,549,804–156,038,680). In addition to a gain of the whole chromosome 8, frequently observed as an additional aberration, in one case SNP array analyses revealed only a partial gain on 8q ranging from 8q24.13 to 8q24.3 (size: 25.3 MB; physical map position 120,986,982–146,268,936). Furthermore, a recurrent deletion (n=2) on chromosome 18 was detected by SNP array but not detected by cytogenetics. The commonly deleted region was localized in 18q23 (size: 3.1 MB; physical map position 72,481,657–75,604,994). In two cases the CBFB-MYH11 rearrangement was cryptic and could not be detected by chromosome banding analysis or FISH using two probes flanking the breakpoints within the CBFB gene, however, a CBFB-MYH11 transcript was amplified by RT-PCR. In one of these cases SNP array data revealed a small gain on 16p13 including 3′ part of the MYH11 gene (size: 71 kb; physical map position 15,654,558–15,725,636) suggesting the insertion of additional 3′ MYH11 sequences into the CBFB rearrangement leading to a CBFB-MYH11 fusion gene. Interestingly, four cases showed a deletion on 16p13 (sizes: 176 kb, 461 kb, 464 kb, 468 kb; physical map positions 15,729,932–15,906,308, 15,726,920–16,188,116, 15,725,663–16,189,984, 15,721,133–16,189,807). All included the 5′ part of the MYH11 gene, and in 3 cases, the ABCC1 gene (multidrug resistance-associated protein 1) was included in the deleted region, which could have an impact on prognosis. The patient with the smallest deletion in 16p13 also showed a deletion on 16q22 including the ′ part of CBFB (size: 35 kb, physical map position 65,672,864–65,707,954). This would be in line with findings in chronic myeloid leukemia where comparable small deletions in the breakpoint region of BCR and ABL have been described. Furthermore, large regions of copy-neutral loss of heterozygosity were observed for the whole short arm of chromosome 1 in two cases, for 17q12 to 17qter and 19q in one case each. In conclusion, a novel mechanism leading to a CBFB-MYH11 fusion gene was identified: A cytogenetically cryptic insertion of additional MYH11 sequences into the CBFB locus. A distinct pattern of additional aberrations was confirmed showing gains of whole chromosomes 8 and 22. Small copy number changes not observable in chromosome banding analysis were detected on 7q, 8q and 18q. A recurrent region of loss of heterozygosity without copy number change was found for the whole short arm of chromosome 1 suggesting that candidate genes in this region are mutated and potentially play a pathogenetic role in AML with CBFB-MYH11-rearrangement.

Rapid prenatal diagnosis of Down syndrome using quantitative fluorescencein situ hybridization on interphase nuclei

2003 ◽  
Vol 23 (2) ◽  
pp. 146-151 ◽  
Author(s):  
Khuong Truong ◽  
Anne Gibaud ◽  
Jean-Michel Dupont ◽  
Marie-N�elle Guilly ◽  
Fran�oise Soussaline ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Prenatal Diagnosis ◽  
Fluorescencein Situ Hybridization ◽  
Interphase Nuclei

scholarly journals Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1

2021 ◽  
Author(s):  
Abigail K. Suwala ◽  
Damian Stichel ◽  
Daniel Schrimpf ◽  
Sybren L. N. Maas ◽  
Martin Sill ◽  
...  
Keyword(s):  
Copy Number ◽  
Molecular Subtype ◽  
Spinal Metastasis ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Chromosome 1 ◽  
Proliferation Index ◽  
Genetic Sequencing ◽  
Dna Methylation Profile ◽  
Frequent Absence

AbstractGlioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations inTP53,RB1andPTEN,with fewer gains of chromosome 7 and homozygousCDKN2A/Bdeletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

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