Identify latent chromosomal aberrations relevant to myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS) are a group of heterogeneous hematologic malignancies. This study aims to identify latent chromosomal abnormalities relevant to MDS, which may optimize the current diagnosis of MDS. Affymetrix CytoScan 750 K microarray platform was utilized to perform a genome-wide detection of chromosomal aberrations in the bone marrow cells of the patients. The findings were compared with the results from traditional karyotypic analysis and FISH to reveal latent chromosomal aberrations. Chromosomal gain, loss, and UPD, and complex karyotypes were identified in those samples. In addition to established cytogenetic aberrations detected by karyotypic analysis, CytoScan 750 K microarray also detected cryptic chromosomal lesions in MDS. Those latent defects underlying multiple gene mutations may construe the clinical variability of MDS. In Conclusion, Affymetrix CytoScan 750 K microarray is efficient in identifying latent chromosomal aberrations in MDS.

Figure 1

Comparison of chromosomal gain detected between MC and microarray. Although MC indicates normal chromosomal 1 in case 8#, Affymetrix Cytoscan 750 K Microarray still reveals cryptic gain(1q21.1-q32.2) with a large size.

Figure 2

Comparison of chromosomal loss detected between MC and microarray. Although MC exhibits normal chromosomal 4 in case 10#, Affymetrix Cytoscan 750 K Microarray still discloses cryptic loss(4q24) with a small size.

Figure 3

UPD disclosed by microarray. Although MC indicates normal chromosome 11, cryptic UPD(11p11.2-pter) in the chromosomal short arm of case 13# is still disclosed by Affymetrix Cytoscan 750 K Microarray.

Figure 4

Validation of genomic aberrations in chromosomal 5. As for 24#, MC revealed del(5)(q13q31), while microarray disclosed gain(5q14.2pter) and loss(5q14.3qter). FISH has validated loss(5q33-34).

Figure 5

The Workflow of Affymetrix Cytoscan 750 K Microarray. QC1 defines DNA concentration ≥ 50ng/µL, OD260/280≈1.9, OD260/230 ≈ 2.0. QC2 defines PCR products on 1% gel electrophoresis should be 150 bp-2000 bp, Purified PCR products ≥ 300 ng/µL, OD260/280 ≈ 1.9, OD260/230≈2.0. QC3 defines fragmentation products on 1% gel electrophoresis should be 25 bp-125 bp. QC4 defines: SNPQC ≥ 15.0; MAPD ≤ 0.25; Waviness SD ≤ 0.12.