High Resolution Genome-Wide Array-Based Comparative Genome Hybridization Reveals Cryptic Chromosome Changes in AML and MDS Cases with Trisomy 8 as the Sole Cytogenetic Aberration.

Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), next to nothing is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML and MDS, cryptic - and possibly primary - genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. To date, however, no such hidden anomalies have been reported. We performed a high resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of ten AML/MDS cases with isolated +8, using an array set containing >30,000 BAC and PAC clones. Array CGH revealed intra-chromosomal imbalances, not corresponding to known genomic polymorphisms, in 5/10 cases, comprising ten duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. Most notably, a 1.8 Mb hemizygous deletion at 7p14.1, which had occurred prior to the +8, was identified in one MDS transforming to AML. Furthermore, a hemizygous deletion at 12p13.2, including ETV6, was present in one case. The remaining eight imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML and MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.