PMID- 26299921 OWN - NLM STAT- MEDLINE DCOM- 20160608 LR - 20190108 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 6 IP - 22 DP - 2015 Aug 7 TI - Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing? PG - 18845-62 AB - 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. FAU - Peterson, Jess F AU - Peterson JF AD - Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA. AD - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. AD - Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Aggarwal, Nidhi AU - Aggarwal N AD - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Smith, Clayton A AU - Smith CA AD - Department of Medicine, Division of Hematology, University of Colorado, Denver, CO. FAU - Gollin, Susanne M AU - Gollin SM AD - Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA. AD - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. AD - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Surti, Urvashi AU - Surti U AD - Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA. AD - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. AD - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Rajkovic, Aleksandar AU - Rajkovic A AD - Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA. AD - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. AD - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. AD - Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Swerdlow, Steven H AU - Swerdlow SH AD - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Yatsenko, Svetlana A AU - Yatsenko SA AD - Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA. AD - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. AD - Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 SB - IM MH - Chromosome Aberrations MH - Chromosome Banding/methods MH - Comparative Genomic Hybridization/methods MH - Cytogenetic Analysis/*methods/standards MH - DNA Copy Number Variations MH - Hematologic Neoplasms/*diagnosis/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence/methods MH - Karyotyping/methods MH - Oligonucleotide Array Sequence Analysis/methods MH - Polymorphism, Single Nucleotide MH - Translocation, Genetic PMC - PMC4662459 OTO - NOTNLM OT - Chromosome Section OT - array CGH OT - diagnosis OT - hematological malignancies OT - microarray COIS- CONFLICTS OF INTEREST The authors declare no conflict of interest. Some of our data were presented as a platform presentation at the 49th Annual Academy of Clinical Laboratory Physicians and Scientists (ACLPS) meeting, San Francisco, CA, May 2014. EDAT- 2015/08/25 06:00 MHDA- 2016/06/09 06:00 PMCR- 2015/08/07 CRDT- 2015/08/25 06:00 PHST- 2015/06/15 00:00 [received] PHST- 2015/07/21 00:00 [accepted] PHST- 2015/08/25 06:00 [entrez] PHST- 2015/08/25 06:00 [pubmed] PHST- 2016/06/09 06:00 [medline] PHST- 2015/08/07 00:00 [pmc-release] AID - 4586 [pii] AID - 10.18632/oncotarget.4586 [doi] PST - ppublish SO - Oncotarget. 2015 Aug 7;6(22):18845-62. doi: 10.18632/oncotarget.4586.