Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for patients with hematologic malignancies

Dougherty, Margaret; Wilmoth, Donna; Tooke, Laura; Shaikh, Tamim H.; Gai, Xiaowu; Hákonarson, Hákon; Biegel, Jaclyn A.

doi:10.1016/j.cancergencyto.2010.10.007

Cited by 29 publications

(38 citation statements)

References 33 publications

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“…It is recognized that CNLOH can generate homozygosity for mutated tumor suppressor genes or oncogenes involved in tumor transformation. For this reason, the majority of studies on hematological neoplasms have been performed using SNP arrays [Dougherty et al, 2011;Dunbar et al, 2008;Hagenkord and Chang, 2009;Heinrichs et al, 2009;Tiu et al, 2009Tiu et al, , 2011b. Initially, the sensitivity for detecting genomic abnormalities in mixed cell population using SNP arrays was rather low due to software limitations, but the sensitivity increased dramatically when the B-allele frequency algorithm was added to the analysis software (Fig.…”

Section: Genome-wide Snp Arraymentioning

confidence: 99%

“…1B). Reliable detection of low-grade clonal mosaicism, at least in the range of 20-30% in leukemic samples, has now been reported [Dougherty et al, 2011;Heinrichs et al, 2010].…”

Section: Genome-wide Snp Arraymentioning

confidence: 99%

“…as chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS), multiple myeloma (MM), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) [Dougherty et al, 2011;Dunbar et al, 2008;Gunnarsson et al, 2011;Hagenkord et al, 2011;Heinrichs et al, 2009;Shao et al, 2010;Simons et al, 2011;Tiu et al, 2009Tiu et al, , 2011aTiu et al, , 2011b. Consequently, array-based molecular karyotyping is slowly but surely finding its way into the clinical laboratories for acquired cytogenetics.…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide arrays in routine diagnostics of hematological malignancies

et al. 2012

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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 genomewide screen in leukemia, and discuss the technical challenges and an interpretation workflow in applying arrays in the acquired cytogenetic diagnostic setting.

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Section: Genome-wide Snp Arraymentioning

confidence: 99%

“…1B). Reliable detection of low-grade clonal mosaicism, at least in the range of 20-30% in leukemic samples, has now been reported [Dougherty et al, 2011;Heinrichs et al, 2010].…”

Section: Genome-wide Snp Arraymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genome-wide arrays in routine diagnostics of hematological malignancies

et al. 2012

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“…Despite significant advances in treatment resulting in a cure rate of nearly 80% in the pediatric population [1][2][3], approximately 20% to 25% of children and more than half of adult patients experience relapse [4,5]. Conventional cytogeneticrearrangements, and hypodiploidy are associated with a poor prognosis [8].…”

Section: Introductionmentioning

confidence: 99%

CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all

Schultz¹,

Tsuchiya²,

Furrow³

et al. 2013

Health

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Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with the majority of cases being of precursor B-cell phenoltype. Conventional cytogenetic analysis plays an important role in the diagnosis of B-cell ALL, identifying characteristic chromosomal abnormalities associated with a given prognosis therein facilitating optimized treatment. The more recent introduction of microarray technology to the analysis of B-cell ALL has afforded both higher resolution for the detection of known abnormalities and an ability to identify novel copy number abnormalities (CNAs) with potential clinical relevance. In the current study, microarray analysis was performed on 20 cytogenetically abnormal B-cell ALL cases (10 pediatric and 10 adult), while a novel microarray-based balancedtranslocation detection methodology (translocation CGH or tCGH) was applied to that subset of cases with a known or suspected recurrent balanced translocation. Standard microarray analysis identified that CNAs was not detected by previous conventional cytogenetics in 75% (15/20) cases. tCGH identified 9/9 (100%) balanced translocations defining BCR/ABL1 (x4), ETV6/RUNX1 (x3), and MLL/AFF1 (x2) breakpoints with high resolution. The results illustrate the improved molecular detail afforded by these technologies and a comparison of translocation breakpoints, CNAs and patient age offers new insights into tumor biology with potential prognostic significance.

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“…Slovak et al 32 revealed, using a genome-wide BAC-based 41 . MDS offers a compelling model for SNP array investigation to uncover novel clonal molecular changes with implications for pathogenesis, evaluation of their effects on disease progression and response to treatment 40 .…”

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confidence: 99%

Molecular genetic methods in the diagnosis of myelodysplastic syndromes. A review

Lukackova¹,

Bujalkova²,

Majerova³

et al. 2014

BIOMED PAP

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Background. Myelodysplastic syndromes (MDS) represent a heterogeneous group of premalignant hematologic disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias and increased risk of progression to acute leukemia. Cytogenetic analysis still plays a central role in the diagnosis of MDS, as clonal chromosomal abnormalities are observed in 30-50% of MDS patients. Despite their technical limitations, standard karyotyping and fluorescence in situ hybridization (FISH) are routinely used for identifying recurrent chromosomal rearrangements. However, using this approach means that submicroscopic and not targeted chromosomal aberrations, as well as somatic mutations and epigenetic changes remain largely undetected. Methods and Results. Introduction of methods for the analysis of copy-number variations (CNV), including arraybased technologies and Multiplex ligation-dependent probe amplification (MLPA) has provided novel insights into the molecular pathogenesis of MDS and considerably extended possibilities for genetic laboratory testing. Several novel molecular markers have been discovered and used for diagnosis and prognostic evaluation of patients with MDS. At present, mutational analysis is not routinely performed, as the clinical significance of somatic mutations in MDS has only begun to emerge. However, recently introduced Next-generation sequencing (NGS) technologies could help to elucidate the relationship between chromosomal and molecular aberrations in MDS and lead to further improvement in its diagnosis. Conclusion. This review focuses on the advantages, limitations, clinical applications and future perspectives of three molecular methods (array-based analysis, MLPA and NGS) currently used in genetic testing and/ or translational research of MDS. In conclusion, a brief summary for clinicians from the routine diagnostic point of view is given.

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Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for patients with hematologic malignancies

Cited by 29 publications

References 33 publications

Genome-wide arrays in routine diagnostics of hematological malignancies

Genome-wide arrays in routine diagnostics of hematological malignancies

CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all

Molecular genetic methods in the diagnosis of myelodysplastic syndromes. A review

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