Advantages of Single Nucleotide Polymorphism(SNP)Array Based Karyotyping in Detection of Chromosomal Defects Combined with Metaphase Cytogenetics in Myelodysplastic Syndromes (MDS)
Authors: Ou Yang , Yu Hongbin , Wu Yu 
Published: November 2019

Background: Metaphase cytogenetics (MC), which has an important diagnostic, prognostic and therapeutic roles in myelodysplastic syndrome (MDS), is widely used as cytogenetic analyzing tools. It can present entire cytogenetic information at one time, although with some limitations such as Hypocellularity, fewer mitotic cells, secondary myelofibrosis and technicians' subjectivity. Single nucleotide polymorphism(SNP)array based karyotyping ( SNP-A based karyotyping) is a novel diagnostic tool which can detect copy number variations with a high resolution. More importantly, SNP-based array has a unique advantage in detection of loss of heterozygosity, also referred as to uniparental disomy (UPD), which results from duplication of a paternal (unimaternal) or maternal (unipaternal) chromosomal region and concurrent loss of the other allele. However the technology is still relatively expensive, and balanced structural
METHOD: We analyzed SNP-A results from 127 patients diagnosed of MDS or MDS related myeloid malignancies(including 6 MDS/MPN, 11 acute myeloid leukemia from MDS, and 110 MDS). 122 patients of them had both MC and SNP-A results. We compared the frequency and diagnostic sensitivity between the cytogenetic aberration findings by MC and genomic alteration findings by SNP-A. In addition, we investigated the novel or additional lesions detected by SNP-A which had not been found by MC, and find further information about the edges of SNP-A. We drew attention to the missing matters of SNP-A which mentioned in MC reports to integrate the limits of SNP-A. We also used multiple-factor analysis to find out the specific situation which MC are not inferior to SNP-A.
RESULTS: There are 199 genomic alteration findings in 127 patients by SNP-A ( including 43 UPDs, 57 gain alterations, 86 loss alterations and 13 complicated alterations). The average length of genomic alterations found by SNP-A is 27795.71Kb, the longest one is GainMosaic(1) (248375kb), the shortest is a UPD found in 17q (41.88Kb). In the 122 patients who had both MC and SNP-A results, SNP-A turns to be more effective than MC in significant chromosomal defects(58.2% vs 36.9%,P<0.005). Novel or additional lesions are detected by SNP-A in patients with normal/noninformative (42.2%) and abnormal(44.4%) MC results. By comparison of the specific results between SNP-A and MC, we found in all 10 complex karyotypes (not less than three cytogenetic aberrations detected by MC), SNP-A could be a more sensitive method to gain more information about particular lesions. Except 10 complex karyotypes, 78 novel or additional lesions in 40 patients could be detected by SNP-A while won't turn up in Metaphase cytogenetics, and these included 38 aberrations of UPD and 33 mosaic deletions or gains. 6 chromosome translocations was detected by MC while not found by SNP-A because of no changes in copy numbers. Two mark DNAs were found in two different patients by MC while SNP-A were negative and need further examination. And combined MC/SNP-A lead to higher diagnostic yield of chromosomal defects, compared MC alone(61.4% vs 37.5%, P<0.005).
CONCLUSIONS: SNP-A based karyotyping seemed to be more sensitive than MC. Because SNP-A based karyotyping have a high throughput to find mosaic deletions or gains and it is the unique metod to detect UPD. SNP-A also can show more information than MC in complex karyotypes.

Disclosures
No relevant conflicts of interest to declare.