Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia

Ouillette, Peter; Collins, Roxane; Shakhan, Sajid; Li, Jinghui; Peres, Edward; Kujawski, Lisa; Talpaz, Moshe; Kaminski, Mark; Li, Cheng; Shedden, Kerby; Malek, Sami N.

doi:10.1182/blood-2010-12-327858

Cited by 101 publications

(117 citation statements)

References 50 publications

(43 reference statements)

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“…Our study showed that even if deletion 13q14 is less frequent in WM than in CLL [26], CLL and WM share a similar MDR on chromosome 13, including micro-RNA genes miRNA-15a, miRNA-16-1, and DLEU7 [21,27]. Herein, we have demonstrated that partial methylation of DLEU7 is a common event in WM independently of 13q deletion, suggesting the role of epigenetic events in WM pathogenesis, that was not observed in normal B cells [16].…”

Section: Discussionmentioning

confidence: 71%

Genome wide SNP array identified multiple mechanisms of genetic changes in Waldenstrom macroglobulinemia

et al. 2013

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SNP array (SNPa) was developed to detect copy number alteration (CNA) and loss of heterozygosity (LOH) without copy number changes, CN-LOH. We aimed to identify novel genomic aberrations using SNPa in 31 WM with paired samples. Methylation status and mutation were analyzed on target genes. A total of 61 genetic aberrations were observed, 58 CNA (33 gains, 25 losses) in 58% of patients and CN-LOH in 6% of patients. The CNA were widely distributed throughout the genome, including 12 recurrent regions and identified new cryptic clonal chromosomal lesions that were mapped. Gene set expression analysis demonstrated a relationship between either deletion 6q or gain of chromosome 4 and alteration of gene expression profiling. We then studied methylation status and sought for mutations in altered regions on target genes. We observed methylation of DLEU7 on chromosome 13 in all patients (n 5 12) with WM, and mutations of CD79B/CD79A genes (17q region), a key component of the BCR pathway, in 15% of cases. Most importantly, higher frequency of 3 CNA was observed in symptomatic WM. In conclusion, this study expands the view of the genomic complexity of WM, especially in symptomatic WM, including a potentially new mechanism of gene dysfunction, acquired uniparental disomy/CN-LOH. Finally, we have identified new potential target genes in WM, such as DLEU7 and CD79A/B. Am. J.

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Section: Discussionmentioning

confidence: 71%

Genome wide SNP array identified multiple mechanisms of genetic changes in Waldenstrom macroglobulinemia

et al. 2013

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“…1 The reason for this appears to be the variability in the clinical course of disease, which could originate from aberrations on a genetic level. 2,3 Moreover, the simultaneous coexistence of two populations of CLL cellsquiescent in peripheral blood and highly proliferative in patient's bone marrow germinal centers, requires therapy effective for both resting and cycling CLL cell populations. [4][5][6] Over the past 20 years, an improvement in CLL treatment has occurred by…”

Section: Introductionmentioning

confidence: 99%

Toward personalized therapy for chronic lymphocytic leukemia

Rogalińska

Franiak-Pietryga

Błoński

et al. 2013

Cancer Biology & Therapy

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“…However, gains of 3q and losses of 1p are relatively frequent in MCL but not in CLL. [14][15][16][17] Gains or trisomy of chromosome 3 are also a frequent feature of marginal zone lymphomas (MZL) and diffuse large B-cell lymphoma (DLBCL) of the activated B-cell subtype (ABC). 18,19 These two types of tumors have frequent gains in 18q but ABC-DLBCL also has frequent deletions in 6q, 9p, and 19q not common in MZL.…”

Section: Platformsmentioning

confidence: 99%

“…15,19 In some lymphoid neoplasms, such as CLL and MCL, DNA-array studies have shown that the genomic complexity is an important prognostic parameter independent of other known factors. [15][16][17] Gene expression profiling The microarray technologies have made possible the study of the global GEP of tumors (Table 2). These platforms consist of numerous DNA probes immobilized on a solid surface.…”

Section: Platformsmentioning

confidence: 99%

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

Campo

2013

Modern Pathology

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The development of high throughput technologies based on the knowledge of the human genome has opened the possibility to search for global genomic alterations in tumors responsible for their development and progression that may have important clinical implications. One of the major applications of this genomic knowledge has been the design of different types of microarray platforms for the analysis of DNA alterations and gene expression profiling (GEP). The main contributions of the DNA studies in lymphoid neoplasms include the definition of relatively characteristic genomic profiles for specific disease entities, the demonstration of common chromosomal alterations across entities, the identification of genes and pathways targeted by the altered chromosomal regions, and the identification of chromosomal alterations with prognostic implications. RNA GEP studies in these tumors have enhanced the molecular characterization of known entities and facilitated the recognition of new subtypes and categories of lymphoid neoplasms, the identification of new biomarkers and prognostic models, and the detection of oncogenic pathways with potential implications for targeted therapies. The recent development of the next generation sequencing (NGS) technologies and its application in lymphoid neoplasms already have provided an initial view of the complex landscape of somatic mutations in these tumors and some findings with important functional and clinical implications. This review addresses the major contributions and limitations of the microarray technologies in the understanding of lymphoid neoplasms and discusses how this knowledge may be transferred into the clinics. The initial results of the NGS studies are also presented.

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Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia

Cited by 101 publications

References 50 publications

Genome wide SNP array identified multiple mechanisms of genetic changes in Waldenstrom macroglobulinemia

Genome wide SNP array identified multiple mechanisms of genetic changes in Waldenstrom macroglobulinemia

Toward personalized therapy for chronic lymphocytic leukemia

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

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