Copy neutral loss of heterozygosity: a novel chromosomal lesion in myeloid malignancies

O’Keefe, Christine L.; McDevitt, Michael A.; Maciejewski, Jaroslaw P.

doi:10.1182/blood-2009-10-201848

Cited by 198 publications

(192 citation statements)

References 76 publications

(79 reference statements)

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“…Results showed that MX did not appear to increase the cytotoxicity observed with fludarabine alone in normal bone marrow cells, presumably, because these cells express lower levels of both UDG and topo II a compared with tumor cells. 7 These results strongly suggest that the induced killing effect of the combination treatment of fludarabine and MX would be selective toward tumor cells, which would be relatively protective of normal bone marrow cells.…”

mentioning

confidence: 75%

“…Based on these observations, it can be postulated that areas of somatic UPD may identify regions that harbor mutations in the regions affected by the copy number neutral loss of heterozygosity/UPD. 7 If found, somatic UPD most often spans large areas of the affected chromosome, thus making identification of mutated target genes quite challenging.…”

Section: Sl Gerson and L Liu Have Conflict Of Interest Tracon Pharmacementioning

confidence: 99%

“…Interestingly, other recurrently deleted areas associated with myeloid malignancies, such as del(20q) and del(5q), are rarely associated with a UPD at the same location. 7 To date, no mutations have been associated with UPD7 in myeloid malignancy, although several of them have been excluded: for example, MET, EPHA1 and BRAF genes. 2 Recent work has identified mutations in an interesting series of genes involved in the modification of chromatin structure and epigenetic regulation in myeloid malignancies.…”

Section: Sl Gerson and L Liu Have Conflict Of Interest Tracon Pharmacementioning

confidence: 99%

“…Previously, we reviewed SNP-A karyograms in a large screen of myeloid malignancies, 7 and identified 15 patients with somatic UPD of the long arm of chromosome 7. This analysis also revealed the presence of several different microdeletions that could define a commonly affected region, and thereby narrow the search for pathogenically mutated genes.…”

Section: Sl Gerson and L Liu Have Conflict Of Interest Tracon Pharmacementioning

confidence: 99%

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Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies

et al. 2010

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confidence: 75%

Section: Sl Gerson and L Liu Have Conflict Of Interest Tracon Pharmacementioning

confidence: 99%

Section: Sl Gerson and L Liu Have Conflict Of Interest Tracon Pharmacementioning

confidence: 99%

Section: Sl Gerson and L Liu Have Conflict Of Interest Tracon Pharmacementioning

confidence: 99%

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Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies

et al. 2010

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“…2 Such arrays would also include probes for recurrent genomic imbalances that are important for tumor classification and prognosis, such as chromosomal deletions at 11q22.3 (ATM), 13q14.3 (MIR15A, MIR16-1), and 17p13.1 (TP53) in chronic lymphocytic leukemia, 74 and deletions involving chromosome 5q and 7q in myeloid stem cell neoplasms. 2 It might also be possible to design tCGH assays that use customized single nucleotide polymorphism arrays for simultaneous identification of balanced translocations, genomic imbalances, copy number-neutral loss of heterozygosity, 75 and point mutations with a single array. Aside from the design of the tCGH array and selection of linear amplification primers, the actual tCGH procedure is very similar to conventional aCGH and takes only ϳ3 hours longer to perform; setup time for the linear amplification reactions is Ͻ15 minutes, run-time on the thermal cycler is ϳ2 hours, and ϳ30 minutes is required to prepare the amplified samples for Cy3/Cy5 labeling.…”

Section: Discussionmentioning

confidence: 99%

Rapid High-Resolution Mapping of Balanced Chromosomal Rearrangements on Tiling CGH Arrays

Greisman

Hoffman

2011

The Journal of Molecular Diagnostics

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The diagnosis and classification of many cancers depends in part on the identification of large-scale genomic aberrations such as chromosomal deletions, duplications, and balanced translocations. Arraybased comparative genomic hybridization (array CGH) can detect chromosomal imbalances on a genome-wide scale but cannot reliably identify balanced chromosomal rearrangements. We describe a simple modification of array CGH that enables simultaneous identification of recurrent balanced rearrangements and genomic imbalances on the same microarray. Using custom tiling oligonucleotide arrays and genespecific linear amplification primers, translocation CGH (tCGH) maps balanced rearrangements to ϳ100-base resolution and facilitates the rapid cloning and sequencing of novel rearrangement breakpoints. As proof of principle, we used tCGH to characterize nine of the most common gene fusions in mature B-cell neoplasms and myeloid leukemias. Because tCGH can be performed in any CGH-capable laboratory and can screen for multiple recurrent translocations and genome-wide imbalances, it should be of broad utility in the diagnosis and classification of various types of lymphomas, leukemias, and solid tumors. ( J Mol Diagn

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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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Copy neutral loss of heterozygosity: a novel chromosomal lesion in myeloid malignancies

Cited by 198 publications

References 76 publications

Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies

Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies

Rapid High-Resolution Mapping of Balanced Chromosomal Rearrangements on Tiling CGH Arrays

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

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