1. ¹Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
2. ²Department of Oncology, Lund University Hospital, Lund, Sweden
3. ³Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden

Correspondence: Dr K Paulsson, Department of Clinical Genetics, University Hospital, Lund SE-221 85, Sweden. E-mail: kajsa.paulsson@med.lu.se

Received 15 November 2005; Revised 12 January 2006; Accepted 17 January 2006; Published online 23 February 2006.

Abstract

Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic – possibly primary – genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing >98% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8 Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.