Comprehensive array CGH of normal karyotype Myelodysplastic syndrome reveals hidden recurrent and individual genomic copy number aberrations with prognostic relevance

About 40% of patients with myelodysplastic syndromes (MDS) present with a normal karyotype and they are facing different courses of disease. To advance the biological understanding and find molecular prognostic markers we performed a high resolution oligonucleotide array study of 107 MDS patients (FAB) with a normal karyotype. Recurrent hidden deletions overlapping with known cytogenetic aberrations or sites of known tumor associated genes were identified in 4q24 (TET2, 2x), 5q31.2 (2x), 7q22.1 (3x) and 21q22.12 (RUNX1, 2x). One patient with a 7q22.1 had an additional 5q31.2 deletion of the AML/MDS region; the smallest deletion identified so far and includes the putative tumor suppressor (ts) genes EGR1 and CTNNA1. One TET2 deletion was homozygous and one heterozygous, with a missense mutation in the remaining allele, further supporting its role as ts gene. Besides these recurrent alterations, additional individual imbalances were found in 34 cases; in total 42/107 (39%) cases had genomic imbalances, deletions were more frequent than gains. These patients had an inferior survival as compared with the rest of the patients (P=0.002). This study emphasizes the heterogeneity of MDS but points to interesting genes which may have diagnostic and prognostic impact. Array CGH experiment, MDS tumor cells vs. control DNA. Total of 107 tumors.