Medical College of Wisconsin
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Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing? Oncotarget 2015 Aug 07;6(22):18845-62

Date

08/25/2015

Pubmed ID

26299921

Pubmed Central ID

PMC4662459

DOI

10.18632/oncotarget.4586

Scopus ID

2-s2.0-84938822208 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

PURPOSE: To evaluate the clinical utility, diagnostic yield and rationale of integrating microarray analysis in the clinical diagnosis of hematological malignancies in comparison with classical chromosome karyotyping/fluorescence in situ hybridization (FISH).

METHODS: G-banded chromosome analysis, FISH and microarray studies using customized CGH and CGH+SNP designs were performed on 27 samples from patients with hematological malignancies. A comprehensive comparison of the results obtained by three methods was conducted to evaluate benefits and limitations of these techniques for clinical diagnosis.

RESULTS: Overall, 89.7% of chromosomal abnormalities identified by karyotyping/FISH studies were also detectable by microarray. Among 183 acquired copy number alterations (CNAs) identified by microarray, 94 were additional findings revealed in 14 cases (52%), and at least 30% of CNAs were in genomic regions of diagnostic/prognostic significance. Approximately 30% of novel alterations detected by microarray were >20 Mb in size. Balanced abnormalities were not detected by microarray; however, of the 19 apparently "balanced" rearrangements, 55% (6/11) of recurrent and 13% (1/8) of non-recurrent translocations had alterations at the breakpoints discovered by microarray.

CONCLUSION: Microarray technology enables accurate, cost-effective and time-efficient whole-genome analysis at a resolution significantly higher than that of conventional karyotyping and FISH. Array-CGH showed advantage in identification of cryptic imbalances and detection of clonal aberrations in population of non-dividing cancer cells and samples with poor chromosome morphology. The integration of microarray analysis into the cytogenetic diagnosis of hematologic malignancies has the potential to improve patient management by providing clinicians with additional disease specific and potentially clinically actionable genomic alterations.

Author List

Peterson JF, Aggarwal N, Smith CA, Gollin SM, Surti U, Rajkovic A, Swerdlow SH, Yatsenko SA



MESH terms used to index this publication - Major topics in bold

Chromosome Aberrations
Chromosome Banding
Comparative Genomic Hybridization
Cytogenetic Analysis
DNA Copy Number Variations
Hematologic Neoplasms
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Translocation, Genetic