Research Papers: Chromosome:

Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing?

Jess F. Peterson _, Nidhi Aggarwal, Clayton A. Smith, Susanne M. Gollin, Urvashi Surti, Aleksandar Rajkovic, Steven H. Swerdlow and Svetlana A. Yatsenko

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Oncotarget. 2015; 6:18845-18862. https://doi.org/10.18632/oncotarget.4586

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Jess F. Peterson1,2,6, Nidhi Aggarwal3, Clayton A. Smith4, Susanne M. Gollin1,2,3, Urvashi Surti1,2,3, Aleksandar Rajkovic1,2,3,5, Steven H. Swerdlow3, Svetlana A. Yatsenko1,3,5

1Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA

2Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

3Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

4Department of Medicine, Division of Hematology, University of Colorado, Denver, CO, USA

5Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

6Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA

Correspondence to:

Svetlana A. Yatsenko, e-mail: [email protected]

Keywords: Chromosome Section, hematological malignancies, microarray, diagnosis, array CGH

Received: June 15, 2015     Accepted: July 21, 2015     Published: July 31, 2015


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.

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