Refined cytogenetic IPSS‐R evaluation by the use of SNP array in a cohort of 290 MDS patients

Abstract

Genetic testing plays a central role in myelodysplastic neoplasms (MDS) diagnosis, prognosis, and therapeutic decisions. The widely applied cytogenetic revised international prognostic scoring system (IPSS‐R) was based on chromosome banding analysis (CBA). However, subsequently developed genetic methodologies, such as single nucleotide polymorphism (SNP) array, demonstrated to be a valid alternative test for MDS. SNP array is, in fact, able to detect the majority of MDS‐associated cytogenetic aberrations, by providing further genomic information due to its higher resolution. In this study, 290 samples from individuals with a confirmed or suspected diagnosis of MDS were tested by both CBA and SNP array, in order to evaluate and compare their cytogenetic IPSS‐R score in the largest MDS cohort reported so far. A concordant or better refined cytogenetic IPSS‐R array‐based score was obtained for 95% of cases (277). Therefore, this study confirms the effective applicability of SNP array toward the cytogenetic IPSS‐R evaluation and consequently, toward the molecular international prognostic scoring system for MDS (IPSS‐M) assessment, which ensures an improved MDS risk stratification refinement. Considering the advent of additional genetic technologies interrogating the whole genome with increased resolutions, counting cytogenetic abnormalities based on their size may result in a simplistic approach. On the contrary, assessing overall genomic complexity may provide additional crucial information. Independently of the technology used, genetic results should indeed aim at ensuring a highly refined stratification for MDS patients.

Parallel genomic analysis from paired bone marrow and peripheral blood samples of 200 cytopenic patients

“…Previously, a high concordance regarding mutational information between BM and PB has been shown (reviewed in [ 4 ]). Unlike mutational concordance between BM and PB, little is known whether cytogenetic information covering the entire genome can reliably be retrieved from PB [ 5 – 7 ]. Chromosome banding analysis (CBA) of BM metaphases represents the gold standard for cytogenetic diagnostics while karyotyping from PB is frequently limited by cytopenia, low blast count, or lack of in vitro proliferation [ 6 ].…”