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From cryptic chromosomal lesions to pathologically relevant genes: Integration of SNP‐array with gene expression profiling in myelodysplastic syndrome with normal karyotype
Author(s) -
Merkerova Michaela Dostalova,
Bystricka Dagmar,
Belickova Monika,
Krejcik Zdenek,
Zemanova Zuzana,
Polak Jaroslav,
Hajkova Hana,
Brezinova Jana,
Michalova Kyra,
Cermak Jaroslav
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.21927
Subject(s) - biology , snp array , genetics , karyotype , gene expression profiling , myelodysplastic syndromes , single nucleotide polymorphism , uniparental disomy , snp genotyping , gene , candidate gene , chromosome , gene expression , genotype , bone marrow , immunology
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. © 2012 Wiley Periodicals, Inc.