A cryptic deletion in 5q31.2 provides further evidence for a minimally deleted region in myelodysplastic syndromes

Victorian Cancer Cytogenetics Service, St. Vincent's Hospital (Melbourne), Fitzroy, VIC, Australia.
Cancer Genetics (Impact Factor: 2.98). 04/2011; 204(4):187-94. DOI: 10.1016/j.cancergen.2011.02.001
Source: PubMed


Recurrent deletions of 5q in myeloid malignancies encompass two separate regions: deletion of 5q33, which is associated with the 5q− syndrome and haploinsufficiency of RPS14, and deletion of a more proximal locus at 5q31. We present a case with a cryptic 1.3 Mb deletion in 5q31.2 identified by array comparative genomic hybridization that places the proximal boundary of the deletion proximal and close to the candidate EGR1 gene. The patient was diagnosed initially with a myelodysplastic syndrome, with a del(20)(q11.2q13.3) as the sole abnormality identified by karyotyping. The patient progressed to acute myeloid leukemia with no change to the G-banded karyotype. The 1.3 Mb deletion on the long arm of one chromosome 5 was confirmed to have been present both at presentation with myelodysplastic syndrome and at transformation. This is an interesting case because there are few array studies identifying cryptic 5q deletions, and the study of these small deletions helps to refine the common deleted region. This case, together with previously published studies, suggests that the proximal boundary of the common deleted region may lie within the KDM3B gene.

9 Reads
  • Source
    • "However, the 5q deletions are highly variable in size and include two different genomic regions, namely, deletions of chromosome band 5q31, encompassing the EGR1 gene, and deletions of bands 5q32 and 5q33 involving haploinsufficiency of RPS14. Molecular karyotyping enables accurate identification of both loci of the 5q deletions, which can be missed when applying only traditional metaphase karyotyping and FISH [MacKinnon et al., 2011]. Furthermore, normal karyotypes are found in 50–60% of the patients, for whom there are no molecular tests to distinguish MDS from benign bone marrow cell diseases making monitoring disease progression in these patients difficult. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the last three decades, cytogenetic analysis of malignancies has become an integral part of disease evaluation and prediction of prognosis or responsiveness to therapy. In most diagnostic laboratories, conventional karyotyping, in conjunction with targeted fluorescence in situ hybridization analysis, is routinely performed to detect recurrent aberrations with prognostic implications. However, the genetic complexity of cancer cells requires a sensitive genome-wide analysis, enabling the detection of small genomic changes in a mixed cell population, as well as of regions of homozygosity. The advent of comprehensive high-resolution genomic tools, such as molecular karyotyping using comparative genomic hybridization or single-nucleotide polymorphism microarrays, has overcome many of the limitations of traditional cytogenetic techniques and has been used to study complex genomic lesions in, for example, leukemia. The clinical impact of the genomic copy-number and copy-neutral alterations identified by microarray technologies is growing rapidly and genome-wide array analysis is evolving into a diagnostic tool, to better identify high-risk patients and predict patients' outcomes from their genomic profiles. Here, we review the added clinical value of an array-based genome-wide screen in leukemia, and discuss the technical challenges and an interpretation workflow in applying arrays in the acquired cytogenetic diagnostic setting.
    Human Mutation 06/2012; 33(6):941-8. DOI:10.1002/humu.22057 · 5.14 Impact Factor
  • Source
    • "Examples of array CGH. A. Images produced using DNA extracted from bone marrow (BM) refrigerated for 1 day (diagnosis specimen of SVH05 [8]), 27 days (AML specimen from [7]) and 36 days. B. Images produced from fixed cytogenetic preparations (CHR) stored at -80°C for one year and 8 years. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The analysis of nucleic acids is limited by the availability of archival specimens and the quality and amount of the extracted material. Archived cytogenetic preparations are stored in many laboratories and are a potential source of total genomic DNA for array karyotyping and other applications. Array CGH using DNA from fixed cytogenetic preparations has been described, but it is not known whether it can be used for SNP arrays. Diagnostic bone marrow specimens taken during the assessment of hematological malignancies are also a potential source of DNA, but it is generally assumed that DNA must be extracted, or the specimen frozen, within a day or two of collection, to obtain DNA suitable for further analysis. We have assessed DNA extracted from these materials for both SNP array and array CGH. We show that both SNP array and array CGH can be performed on genomic DNA extracted from cytogenetic specimens stored in Carnoy's fixative, and from bone marrow which has been stored unfrozen, at 4°C, for at least 36 days. We describe a procedure for extracting a usable concentration of total genomic DNA from cytogenetic suspensions of low cellularity. The ability to use these archival specimens for DNA-based analysis increases the potential for retrospective genetic analysis of clinical specimens. Fixed cytogenetic preparations and long-term refrigerated bone marrow both provide DNA suitable for array karyotyping, and may be suitable for a wider range of analytical procedures.
    Molecular Cytogenetics 02/2012; 5(1):10. DOI:10.1186/1755-8166-5-10 · 2.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Harmonic distortion on the power system is a modern concern due to the technological advances in silicon technology and it presents an increased non-linear loading of the power system. The effects of harmonics are well known: customers could experience major production losses due to the loss of supply, for example; on the other hand, harmonic load currents cause the utility to supply a higher real energy input then the actual real power needed to maintain a plant's production at a certain level. The utility carries the extra transmission I<sup>2 </sup>R losses due to the harmonic currents. Consequently, the installed power system capacity is higher then required for a comparable linear load. Traditional energy rates do not take into account these extra costs. A tariff system may be one solution to regulate the total harmonic pollution in a power system. Different tariff strategies are evaluated and it is shown that they can allocate the increased costs more fairly than current rate structures
    AFRICON, 2004. 7th AFRICON Conference in Africa; 10/2004
Show more