title: From cryptic chromosomal lesions to pathologically relevant genes: integration of SNP-array with gene expression profiling in myelodysplastic syndrome with normal karyotype.
abstract: Myelodysplastic syndrome (MDS), a clonal disorder originating from hematopoietic stem cell, is characterized by a progressive character often leading to transformation to acute myeloid leukemia. We used single nucleotide polymorphism arrays (SNP-A) to identify previously cryptic chromosomal abnormalities such as copy number alterations and uniparental disomies (UPD) in cytogenetically normal MDS. In the aberrant regions, we attempted to localize candidate genes with potential relevance to the disease. Using SNP-A, we analyzed peripheral blood granulocytes from 37 MDS patients. The analysis identified 13 cryptic chromosomal defects in 10 patients (27%). Four UPD (affecting chromosomes 3q, 7q, 17q, and 20p), 5 deletions and 4 duplications were detected. Gene expression data measured on CD34+ cells were available for 4 patients with and 6 patients without SNP-A lesions. We performed an integrative analysis of genotyping and gene expression microarrays and found several genes with an altered expression located in the aberrant regions. The expression microarrays suggested BMP2 and TRIB3 located in 20p UPD as potential candidate genes contributing to MDS. We showed that the genome-wide integrative approach is beneficial to the comprehension of molecular backgrounds of diseases with incompletely understood etiopathology.
authors.affiliation: Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. michaela.merkerova@uhkt.cz
authors.forename: Michaela Dostalova
authors.initials: MD
authors.lastname: Merkerova
authors.forename: Dagmar
authors.initials: D
authors.lastname: Bystricka
authors.forename: Monika
authors.initials: M
authors.lastname: Belickova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Krejcik
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Polak
authors.forename: Hana
authors.initials: H
authors.lastname: Hajkova
authors.forename: Jana
authors.initials: J
authors.lastname: Brezinova
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D016019:Survival Analysis; D055815:Young Adult