Molecular cytogenetic analysis of genomic instability at the 1q12-22 chromosomal site in B-cell non-Hodgkin lymphoma

Abnormalities of chromosome arm Iq have frequently been reported in B-cell non-Hodgkin lymphoma (NHL), and correlated with poor outcome. Five genes mapped to this region (BCL9, MUC1, FCGR2B, IRTA1, and RTA2) have been shown to be deregulated by juxtaposition with the IG genes. However, abnormalities of the Iq21-22 region that are not involved in translocations with the IG genes have not been addressed. We performed a molecular cytogenetic analysis of Iq12-22 abnormalities in 24 B-cell NHL cases. The cases analyzed were in two groups: one, composed of 18 cases with the single break in the Iq12-22 region, and another, composed of six cases with multiple breaks in the Iq12-22 region. The involvement of heterochromatin and its vicinity was observed most frequently in the single-break cases (13 of 18 cases). In this group, the recurring partner region was Iq32, which resulted in dup(1)(q12-21q32) or trp(l)(q12q32) in 5 cases. The 6 cases with multiple breaks showed an unexpected level of instability along with complex combinations of abnormalities, especially sequential duplication and inversion, in the Iq12-22 region. The BCL9 locus was deleted by complex aberration in 2 of 6 cases. High-level amplification of the WI-16757 locus was found in 2 cases. Our studies demonstrate a high level of instability of the Iq12-22 region, possibly stemming from its chromatin organization. Chromosome arm Iq is gene-rich, and characterization of aberrations described in this study can be expected to lead to the discovery of additional functionally significant genetic changes. (C) 2002 Wiley-Liss, Inc.