The rewards and challenges of array-based karyotyping for clinical oncology applications

Hagenkord, Jill; Chang, Chung Che

doi:10.1038/leu.2009.24

Cited by 17 publications

(24 citation statements)

References 34 publications

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“…The aUPD converted the original heterozygous deletion at 13q14 to a homozygous deletion with identical break points on both alleles (Figure 4, CLL27). 3 Thus the aUPD of 13q reflects clonal evolution, and it was detected by FISH as a homozygous deletion of 13q14 in both cases. However, depending on the break point on each allele (see Figure 4), clonal evolution at the 13q14 locus may or may not be detected by a single FISH probe.…”

Section: The Importance Of Acquired Uniparental Disomy In Cancermentioning

confidence: 99%

“…In addition, we have incorporated B-cell enrichment before DNA extraction. 3 In our hands, enrichment for B cells enables more equitable comparisons of log2ratios among samples and also helps resolve lesions in samples with low tumor burden or small subclones. With these optimizations, the sensitivity of SNP array karyotyping approaches that of FISH for CLL prognostic assessment while retaining its additional advantages.…”

Section: Tumor Burden and Software Considerationsmentioning

confidence: 99%

“…A demonstration of the effectiveness of B cell enrichment for CLL has been published elsewhere. 3 For samples undergoing enrichment, the average estimated percentage of CLL cells present in the sample post enrichment was 80% (57% to 89%). If the other samples in our cohort had undergone enrichment before DNA extraction, the average percentage of CLL cells would have been 79% (53% to 87%).…”

Section: Effect Of Array Density On Ability To Detect Clinically Relementioning

confidence: 99%

“…CLL is an ideal neoplasm to study with copy number arrays because 1) the genetic lesions with known clinical relevance are chromosomal gains and losses rather than balanced translocations and inversions, 2) DNA from a fresh sample is generally available, making the analysis more straightforward than for formalin-fixed paraffin embedded tissue, 3) tumor burden is known from the flow cytometry results and can help guide downstream analysis, 4) tumor burden tends to be relatively high in the peripheral blood, and 5) enrichment for B lymphocytes or CLL cells is simple, cost-effective, amenable to routine clinical use, and minimizes the effect of 'normal clone contamination.' 3 Array-based karyotyping can be done with several different platforms. The arrays themselves can be genome-wide (probes distributed over the entire genome) or targeted (probes for genomic regions known to be involved in a specific disease) or a combination of both.…”

mentioning

confidence: 99%

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Array-Based Karyotyping for Prognostic Assessment in Chronic Lymphocytic Leukemia

Hagenkord

Monzon

Kash

et al. 2010

The Journal of Molecular Diagnostics

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Section: The Importance Of Acquired Uniparental Disomy In Cancermentioning

confidence: 99%

Section: Tumor Burden and Software Considerationsmentioning

confidence: 99%

Section: Effect Of Array Density On Ability To Detect Clinically Relementioning

confidence: 99%

mentioning

confidence: 99%

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Array-Based Karyotyping for Prognostic Assessment in Chronic Lymphocytic Leukemia

Hagenkord

Monzon

Kash

et al. 2010

The Journal of Molecular Diagnostics

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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%

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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Microarray‐based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia

Simons

Stevens‐Kroef

Idrissi-Zaynoun

et al. 2011

Genes Chromosomes & Cancer

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In acute lymphoblastic leukemia (ALL) specific genomic abnormalities provide important clinical information. In most routine clinical diagnostic laboratories conventional karyotyping, in conjunction with targeted screens using e.g., fluorescence in situ hybridization (FISH), is currently considered as the gold standard to detect such aberrations. Conventional karyotyping, however, is limited in its resolution and yield, thus hampering the genetic diagnosis of ALL. We explored whether microarray-based genomic profiling would be feasible as an alternative strategy in a routine clinical diagnostic setting. To this end, we compared conventional karyotypes with microarray-deduced copy number aberration (CNA) karyotypes in 60 ALL cases. Microarray-based genomic profiling resulted in a CNA detection rate of 90%, whereas for conventional karyotyping this was 61%. In addition, many small (< 5 Mb) genetic lesions were encountered, frequently harboring clinically relevant ALL-related genes such as CDKN2A/B, ETV6, PAX5, and IKZF1. From our data we conclude that microarray-based genomic profiling serves as a robust tool in the genetic diagnosis of ALL, outreaching conventional karyotyping in CNA detection both in terms of sensitivity and specificity. We also propose a practical workflow for a comprehensive and objective interpretation of CNAs obtained through microarray-based genomic profiling, thereby facilitating its application in a routine clinical diagnostic setting.

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The rewards and challenges of array-based karyotyping for clinical oncology applications

Cited by 17 publications

References 34 publications

Array-Based Karyotyping for Prognostic Assessment in Chronic Lymphocytic Leukemia

Array-Based Karyotyping for Prognostic Assessment in Chronic Lymphocytic Leukemia

Genome-wide arrays in routine diagnostics of hematological malignancies

Microarray‐based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia

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