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

Leukemia volume 25, pages 387–399 (2011)Cite this article

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Abstract

About 40% of patients with myelodysplastic syndromes (MDSs) present with a normal karyotype, and they are facing different courses of disease. To advance the biological understanding and to find molecular prognostic markers, we performed a high-resolution oligonucleotide array study of 107 MDS patients (French American British) with a normal karyotype and clinical follow-up through the Duesseldorf MDS registry. 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 deletion had an additional 5q31.2 deletion of the acute myeloid leukemia/MDS region, the smallest deletion identified so far and including 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 a ts gene. Besides these recurrent alterations, additional individual imbalances were found in 34 cases; in total, 42/107 (39%) cases had genomic imbalances. 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 that may have diagnostic and prognostic impact.

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Acknowledgements

This work was supported by a grant from the Wilhelm Sander Stiftung 2008.027.1 (BR-P) and a grant from the Forschungskommission HHU Duesseldorf 11/06 (CE and BB).

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  1. C Evers

    Present address: 3Current address: Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.,

Authors and Affiliations

  1. Institute of Human Genetics and Anthropology, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany

    A Thiel, M Beier, D Ingenhag, K Servan, M Hein, V Moeller, B Betz, B Hildebrandt, C Evers & B Royer-Pokora

  2. Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Duesseldorf, Germany

    U Germing

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Correspondence to B Royer-Pokora.

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Thiel, A., Beier, M., Ingenhag, D. et al. Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance. Leukemia 25, 387–399 (2011). https://doi.org/10.1038/leu.2010.293

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