Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes

Abstract

Low-risk myelodysplastic syndrome (MDS

Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies

“…Although karyotyping analysis with SNP-A have been used in the past, 34 the current study differs in several important and critical aspects compared with the initial report by Gondek et al 14 and Mohamedali et al 18 First, this study emphasizes the complementary usage of both MC and SNP-A, whereas the original studies of For personal use only. on May 11, 2018.…”

“…14,18 Our protocol involved exclusion of known nonclonal germline-encoded CNVs and CN-LOH and the confirmation of new somatic defects with the use of paired nonclonal cells (supplemental Figure 1A-B). We performed SNP-A 6.0 arrays on 228 samples, 250K arrays on 200 samples and 50K arrays in 2 samples.…”

“…13,14 Hybridization of tumor DNA to arrays containing probes specific for allelic variants of SNPs allows for measurement of gene copy number (hybridization signal intensity) and distinction of individual genotypes for detection of loss of heterozygosity (LOH) at a high resolution. SNP-A-based karyotyping has been applied previously in a range of studies that used a limited number of patients with various hematologic malignancies, [12][13][14][15][16][17][18] all with similar end-point data, suggesting its potential clinical utility. In addition to a high level of resolution, SNP-A allows for a better appreciation of acquired copy-neutral LOH (aCN-LOH), also referred to as somatic uniparental disomy, a common chromosomal defect in hematologic malignancies, undetectable by conventional MC.…”

Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance

“…One SNP array study of 119 lowrisk MDS patients, 77 with a normal karyotype, 36 with visible cytogenetic alterations and 6 with unavailable cytogenetics, identified 125 UPDs with a median size of 3.78 Mb in 46% of the cases studied. 8 Another study showed that 82% of MDS patients harbor gains and losses detected by SNP arrays, whereas conventional cytogenetics detected alterations in 50%. 9 In addition, UPD was found in 33% of the patients.…”

“…In both studies, first correlations of genomic imbalances including UPD with survival indicated that the presence of these may correlate with a shorter survival. 8,9 This high rate of UPDs in MDS was recently challenged in a study that showed, when using buccal DNA samples from the same patients as controls, that only a small number of the potential loss of heterozygosity regions represent tumor-specific UPDs and gains and losses. 10 In that report only 4/33 cytogenetically normal cases had additional alterations.…”