High-resolution genomic and expression analyses of copy number alterations in breast tumors

2008 ◽  
Vol 47 (6) ◽  
pp. 530-542 ◽  
Author(s):  
Peter M. Haverty ◽  
Jane Fridlyand ◽  
Li Li ◽  
Gad Getz ◽  
Rameen Beroukhim ◽  
...  
Keyword(s):  
High Resolution ◽  
Copy Number ◽  
Breast Tumors ◽  
Copy Number Alterations

Genome-Wide High-Resolution Screening in Dupuytren's Disease Reveals Common Regions of DNA Copy Number Alterations

2010 ◽  
Vol 35 (7) ◽  
pp. 1172-1183.e7 ◽  
Author(s):  
Barbara B. Shih ◽  
May Tassabehji ◽  
James S. Watson ◽  
Angus D. McGrouther ◽  
Ardeshir Bayat
Keyword(s):  
High Resolution ◽  
Copy Number ◽  
Dupuytren’S Disease ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
Dupuytren's Disease ◽  
Genome Wide ◽  
Dna Copy Number Alterations

High Resolution Screening of Copy-Number Alterations in Chronic Lymphocytic Leukemia Using Affymetrix 250K SNP-Arrays Reveals a Higher Complexity of Genomic Alterations in Patients with Unmutated IGHV Genes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3133-3133
Author(s):  
Rebeqa Gunnarsson ◽  
Anders Isaksson ◽  
Hanna Göransson ◽  
Larry Mansouri ◽  
Mattias Jansson ◽  
...  
Keyword(s):  
High Resolution ◽  
Copy Number ◽  
Average Length ◽  
Lymphocytic Leukemia ◽  
Copy Number Alterations ◽  
Snp Arrays ◽  
Genetic Complexity ◽  
Trisomy 12 ◽  
Allelic Deletion ◽  
Gains And Losses

Abstract Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous disease where no common genetic aberration so far has been described. Although recurrent genomic aberrations of prognostic significance are well established (e.g. deletions of 11q, 13q, 17p and trisomy 12), less is known about the overall genetic complexity. Recent development of high-resolution single nucleotide polymorphism (SNP)-arrays will allow screening of genetic complexity, which includes detection of smaller copy-number alterations (CNAs) in addition to the known, recurrent aberrations. We here applied the Affymetrix GeneChip® Mapping 250K Nsp arrays and screened peripheral blood samples from 203 newly diagnosed CLL patients (≥70% tumor cells) from a population-based Scandinavian cohort. The male:female ratio was 2:1, the majority of patients was in stage A (70%) and the median age at diagnosis 61 years. Sixty percentage of cases displayed mutated IGHV genes whereas 35% showed unmutated IGHV genes. The Nexus copy-number software (Biodiscovery, Inc.) was applied and CNAs were identified in all CLL samples investigated, where deletions were more commonly detected than gains (in average, 3.5 vs. 2.2 per sample, respectively). The average length of deletions was 3.5 Mb while gains had an average length of 9.5 Mb (3.6 Mb when excluding trisomy 12). More than 50% of deletions and gains had a size ranging between 0.1–1 Mb, whereas 22% of CNAs were less than 0.1 Mb and 25% larger than 1 Mb. When investigating known, recurrent alterations, 105 samples (52%) carried del(13)(q14); 82 samples displayed a mono-allelic deletion, 15 samples a bi-allelic deletion and 8 samples carried 2 mono-allelic deletions of different sizes. The minimal overlapping region was 0.44 Mb and most of the 13q14 deletions covered the genomic region of miR-15, miR-16 and/or DLEU7. Twenty-one samples (10%) showed trisomy 12 and del(11q) was detected in 27 samples (13%), all covering the ATM gene. del(17p) was detected in 7 patients (3.4%) with one patient also carrying several gains and losses of 17q. Moreover, large alterations involving chromosome arms or entire chromosomes were recurrently observed among the samples, for instance, 3 large 8p losses and 4 large 8q gains. Interestingly, 5 samples, which all carried del(11q), displayed a gain covering whole or large parts of the p-arm of chromosome 2, a region which covers MYCN, REL and BCL11A. Furthermore, comparison of samples with different IGHV mutation status (M vs. UM) illustrated a significantly higher frequency of del(11q) (32% of UM vs. 4% of M), trisomy 12 (22% of UM vs. 5% of M) and gain of 2p (12% vs. 0% in M) in samples with unmutated IGHV genes. As expected, patients with mutated IGHV genes showed a higher frequency of del(13q) (61% of M vs. 31% of UM). In addition, large aberrations (>1Mb) were more common in UM samples which in average displayed 0.57 gains and 1.22 deletions compared to 0.26 gains and 0.67 deletions in M samples. In conclusion, with whole-genome screening using high resolution SNP-arrays, higher complexity was revealed in CLL, including a higher number of gains and losses and a higher frequency of larger aberrations in UM compared to M samples. A novel, recurrent combination of del(11q) and gain of 2p was demonstrated which deserves further investigation.

High-resolution analysis of DNA copy number alterations in rectal cancer

2014 ◽  
Vol 190 (11) ◽  
pp. 1028-1036 ◽  
Author(s):  
Jérôme Doyen ◽  
Eric Letouzé ◽  
Laetitia Marisa ◽  
Aurélien de Reyniès ◽  
Gérard Milano ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Resolution ◽  
Copy Number ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
High Resolution Analysis ◽  
Resolution Analysis ◽  
Dna Copy Number Alterations

Disclosure of Copy Number Alterations in AML with Normal Karyotype Using Matrix-Based Comparative Genomic Hybridization.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 759-759
Author(s):  
Frank G. Rucker ◽  
Lars Bullinger ◽  
Hans A. Kestler ◽  
Peter Lichter ◽  
Konstanze Dohner ◽  
...  
Keyword(s):  
Molecular Markers ◽  
High Resolution ◽  
Comparative Genomic Hybridization ◽  
Copy Number ◽  
Normal Karyotype ◽  
Comparative Genomic ◽  
Copy Number Alterations ◽  
Genomic Hybridization ◽  
Genomic Imbalances ◽  
Genome Wide

Abstract Clonal chromosome abnormalities represent one of the most important prognostic factors in adult acute myeloid leukemia (AML), and cytogenetic data are used for risk-adapted treatment strategies. By conventional cytogenetic analysis, approximately 50% of patients lack clonal chromosome aberrations, and normal cytogenetics are associated with an intermediate clinical outcome. This clinically heterogeneous group seems to be in part characterized by molecular markers, such as MLL, FLT3, CEBPA, and NPM1 mutations. In order to identify novel candidate regions of genomic imbalances, we applied comparative genomic hybridization to microarrays (matrix-CGH). Using this high-resolution genome-wide screening approach we analyzed 49 normal karyotype AML cases characterized for the most common clinically relevant molecular markers (MLL-PTD n=13, FLT3-ITD n=7, FLT3-ITD/NPM1+ n=4, MLL-PTD/FLT3-ITD n=3, CEBPA+ n=12, CEBPA+/FLT3-ITD n=1; CEBPA+/NPM1+ n=1; no molecular markers n=8) with a microarray platform consisting of 2799 different BAC or PAC clones. A set of 1500 of these clones covers the whole human genome with a physical distance of approximately 2 Mb. The remaining 1299 clones either contiguously span genomic regions known to be frequently involved in hematologic malignancies (e.g., 1p, 2p, 3q, 7q, 9p, 11q, 12q, 13q, 17p, 18q) (n=600) or contain oncogenes or tumor suppressor genes (n=699). In addition to known copy number polymorphisms in 5q11, 7q22, 7q35, 14q32, and 15q11, the CLuster Along Chromosomes method (CLAC; http://www-stat.stanford.edu/~wp57/CGH-Miner) disclosed copy number alterations (CNAs) in terms of gains in 1p, 11q, 12q, and 17p. CNAs in terms of losses were identified in 9p, 11q, 12p, 12q, and 13q. Two-class supervised analyses using the significance analysis of microarrays (SAM) method identified for the MLL-PTD cases a gain of a single clone harboring the MLL gene. While the significance of these findings, which are currently validated using fluorescence in-situ hybridization (FISH), still remains to be determined, our preliminary results already demonstrate the power and reliablity of this microarray-based technique allowing genome-wide screens of genomic imbalances as the MLL aberration was detected in all cases known to have a MLL-PTD. Furthermore, ongoing correlation of high-resolution genomic profiling with global gene expression studies will help to disclose pathways underlying normal karyotype AML, thereby leading to new insights of leukemogenesis.

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