FISH and SNP-A karyotyping in myelodysplastic syndromes: Improving cytogenetic detection of del(5q), monosomy 7, del(7q), trisomy 8 and del(20q)

Makishima, Hideki; Rataul, Manjot; Gondek, Lukasz P.; Huh, Jungwon; Cook, James R.; Theil, Karl S.; Sekeres, Mikkael A.; Kuczkowski, Elizabeth; O’Keefe, Christine; Maciejewski, Jaroslaw P.

doi:10.1016/j.leukres.2009.08.023

« Previous Next »Leukemia Research
Volume 34, Issue 4 , Pages 447-453, April 2010

FISH and SNP-A karyotyping in myelodysplastic syndromes: Improving cytogenetic detection of del(5q), monosomy 7, del(7q), trisomy 8 and del(20q)

Hideki Makishima
- Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA
Manjot Rataul
- Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA
Lukasz P. Gondek
- Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA
Jungwon Huh
- Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA
- Department of Laboratory Medicine, Ewha Womans University School of Medicine, Seoul, South Korea
James R. Cook
- Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA
Karl S. Theil
- Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA
Mikkael A. Sekeres
- Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Cleveland, OH, USA
Elizabeth Kuczkowski
- Celgene Corporation, Summit, NJ, USA
Christine O’Keefe
- Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA
Jaroslaw P. Maciejewski
- Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA
- Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Cleveland, OH, USA
- Corresponding author at: Department of Translational Hematology and Oncology Research, Taussig Cancer Center/R40, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel.: +1 216 445 5962; fax: +1 216 636 2498.

Received 20 April 2009; received in revised form 15 August 2009; accepted 17 August 2009. published online 07 March 2011.

Abstract

Cytogenetic aberrations identified by metaphase cytogenetics (MC) have important diagnostic, prognostic and therapeutic roles in myelodysplastic syndromes (MDS). Fluorescence in situ hybridization (FISH) complements MC by the ability to evaluate large numbers of both interphase and metaphase nuclei. However, clinically practical FISH strategies are limited to detection of known lesions. Single nucleotide polymorphism array (SNP-A)-based karyotyping can reveal unbalanced defects with superior resolution over MC and FISH and identify segmental uniparental disomy (UPD) undetectable by either method. Using a standardized approach, we focused our investigation on detection of −5/del(5q), −7/del(7q), trisomy 8 and del(20q) in patients with MDS (N=52), MDS/myeloproliferative overlap syndromes (N=7) and acute myeloid leukemia (N=15) using MC, FISH and SNP-A karyotyping. The detection rate for del(5q) was 30, 32 and 32% by MC, FISH, and SNP-A, respectively. No single method detected all defects, and detection rates improved when all methods were used. The rate for detection of del(5q) increased incrementally to 35% (MC+FISH), 38% (MC+SNP-A), 38% (FISH+SNP-A) and 39% (all three methods). Similar findings were observed for −7/del(7q), trisomy 8 and −20/del(20q). We conclude that MC, FISH and SNP-A are complementary techniques that, when applied and interpreted together, can improve the diagnostic yield for identifying genetic lesions in MDS and contribute to the better description of abnormal karyotypes.