Single nucleotide polymorphism array-based karyotyping in acute myeloid leukemia or myelodysplastic syndrome with...

The clinical heterogeneity of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with trisomy 8 as the sole abnormality may result from cytogenetically undetectable genetic changes. The purpose of this study was to identify hidden genomic aberrations not detected by metaphase cytogenetics (MC) using high-resolution single nucleotide polymorphism array (SNP-A)-based karyotyping in AML/MDS patients with a sole trisomy 8. The study group included 8 patients (3 AML and 5 MDS) and array-based karyotyping was done using whole-genome SNP-A (SNP 6.0 and SNP 2.7M). By SNP-A, additional genomic aberrations not detected by MC were identified in 2 patients: 1 AML patient exhibited a copy-neutral loss of heterozygosity (CN-LOH) of 3q21.1-q29 and 11q13.1-q25 and the other patient with MDS (refractory cytopenia with unilineage dysplasia) had CN-LOH of 2p25.3-p15. In particular, the latter patient progressed to AML 18 months after the diagnosis. In 3 patients, aberrations in addition to trisomy 8 were not identified by SNP-A. In the remaining 3 patients, SNP-A could not detect trisomy 8, while trisomy 8 was found in 25-67% of metaphase cells by MC. This study suggests that additional genomic aberrations may in fact be present even in cases of trisomy 8 as sole abnormality by MC, and SNP-A could be a useful karyotyping tool to identify hidden aberrations such as CN-LOH.