title: FISH and SNP-A karyotyping in myelodysplastic syndromes: improving cytogenetic detection of del(5q), monosomy 7, del(7q), trisomy 8 and del(20q).
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.
authors.affiliation: Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Manjot
authors.initials: M
authors.lastname: Rataul
authors.forename: Lukasz P
authors.initials: LP
authors.lastname: Gondek
authors.forename: Jungwon
authors.initials: J
authors.lastname: Huh
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.forename: Karl S
authors.initials: KS
authors.lastname: Theil
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kuczkowski
authors.forename: Christine
authors.initials: C
authors.lastname: O'Keefe
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002890:Chromosomes, Human, Pair 20; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D008297:Male; D008875:Middle Aged; D009006:Monosomy / Q000175:diagnosis; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014314:Trisomy / Q000175:diagnosis; D055815:Young Adult