Interstitial del(14)(q) involving IGH: a novel recurrent aberration in B-NHL

Using high-resolution array comparative genomic hybridization, we mapped del(14)(q) in a series of 23 B-cell leukemia/lymphoma cases. Interestingly, 14 cases with interstitial del(14)(q) showed involvement of IGH at 14q32.33. Whereas the proximal breakpoints of these deletions varied in 6 cases, they clustered in the 14q24.1/ZFP36L1 region in the 8 remaining cases. The latter del(14)(q24.1q32.33) covering approximately 36 Mb was further demonstrated in 12 additional patients by FISH. The majority of cases harboring this deletion were diagnosed as chronic lymphocytic leukemia (CLL) (75%), particularly atypical CLL, and were frequently associated with trisomy 12 (40%) and unmutated VH region (75%). Further analysis of the 14q32.33 breakpoints showed clustering in the constant region of IGH, proximal to the 5’ (Eµ) enhancer sequences. These findings therefore suggest that the del(14)(q24.1q32.33), and other analogous IGH-involving del(14)(q), might represent a novel aberration leading to activation of unknown oncogene(s) at 14q by its juxtaposition with regulatory elements of IGH. Extensive expression analysis via quantitative PCR and microarray profiling, however, failed to identify a gene uniformly upregulated in cases with del(14)(q24.1q32.33). Further investigations are needed to unravel the mechanism(s) and role of IGH-involving del(14)(q) in B-cell malignancies. Keywords: comparative genomic hybridization 23 lymphocyte samples of B-NHL (B-cell non-Hodgkin lymhomas) were compared to lymphocyte samples of normal individuals. All experiments were carried out in sex-mismatch fashion.