A large fraction of trisomy 12, 17p − , and 11q − CLL cases carry unidentified microdeletions of miR-15a/16-1

Significance 13q14.3 deletion is the most common genetic lesion identified in CLLs. This study shows that microdeletions affecting the miR-15a/16-1 cluster are more frequent than expected in all CLL cohorts and are prevalent in patients carrying a trisomy 12. Copy-number variation analysis and an experimental FISH analysis revealed that ∼34% of samples carry previously unidentified microdeletions of miR-15a/16-1. These data may have clinical relevance for the successful stratification of patients for treatment.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by chromosomal aberrations including 13q, 11q, and 17p deletions and a trisomy of chromosome 12 (T12). 13q deletions are often associated with 11q and 17p deletions in aggressive cases. Conversely, T12 CLLs show a variable prognosis, and association with 13q deletions is uncommon. The miR-15a/16-1 cluster is the functional target of 13q deletions, leading to BCL2 overexpression. Chromosomal aberrations in CLL are associated with prognosis, and their identification is carried out by fluorescence in situ hybridization (FISH). Since standard FISH only detects large deletions, we investigated the presence of undetected microdeletions targeting miR-15a/16-1 in CLL cases. We found that ∼34% of CLL samples show an unreported loss of the miR-15a/16-1 locus regardless of their cytogenetic profile. Interestingly, 15 out of 39 (∼39%) of all CLLs with T12, carry microdeletions of miR-15a/16-1, indicating that, in patients with T12, miR-15a/16-1 are mostly inactivated by microdeletions. In addition, ∼40% of CLL cases bearing T12, 17p−, and 11q− showed unidentified microdeletions of miR-15a/16-1, suggesting that miR-15a/16-1 loss cooperates with such chromosomal alterations in CLL. These data may have clinical relevance for the successful stratification of patients for treatment.