The IgG Fc receptor, FcγRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma

Abstract

Rearrangement of chromosomal bands 1q21–23 is one of the most frequent chromosomal aberrations observed in hematological malignancy. The genes affected by these rearrangements remain poorly characterized. Typically, 1q21–23 rearrangements arise during tumor evolution and accompany disease-specific chromosomal rearrangements such as t(14;18) ( BCL2 ) and t(8;14) ( MYC ), where they are thus thought to play an important role in tumor progression. The pathogenetic basis of this 1q21–23-associated disease progression is currently unknown. In this setting, we surveyed our series of follicular lymphoma for evidence of recurring 1q21–23 breaks and identified three cases in which a t(14;18)(q32;q21) was accompanied by a novel balanced t(1;22)(q22;q11). Molecular cloning of the t(1;22) in a cell line (B593) derived from one of these cases and detailed fluorescent in situ hybridization mapping in the two remaining cases identified the FCGR2B gene, which encodes the immunoreceptor tyrosine-based inhibition motif-bearing IgG Fc receptor, FcγRIIB, as the target gene of the t(1;22)(q22;q11). We demonstrate deregulation of FCGR2B leading to hyperexpression of FcγRIIb2 as the principal consequence of the t(1;22). This is evidence that IgG Fc receptors can be targets for deregulation through chromosomal translocation in lymphoma. It suggests that dysregulation of FCGR2B may play a role in tumor progression in follicular lymphoma.

Case of acute lymphoblastic leukemia presenting with t(14;18)/BCL2, t(8;14)/cMYC, and t(1;2)/FCGR2B

“…Rearrangement of chromosomal band 1q21-23 is one of the most common secondary alternations associated with B-cell NHL [16,17], yet only six have been characterized to date. Three of these were shown by Callanan et al [18] to deregulate the IgGFc receptor, FcgRllB. We have shown by Southern blotting, using a probe (EC2) specific for the FCGR2 genes [18], that this locus is also altered in the patient described here.…”

“…Three of these were shown by Callanan et al [18] to deregulate the IgGFc receptor, FcgRllB. We have shown by Southern blotting, using a probe (EC2) specific for the FCGR2 genes [18], that this locus is also altered in the patient described here. This finding adds support to the possibility that deregulation of this gene can be related to the development of lymphoma/leukemia.…”

Genomic organization of classical human low-affinity Fcγ receptor genes

“…They establish a dense SNP map which will facilitate the discovery of genetic variations underlying susceptibility to autoimmune and other diseases. They indicate that the chromosome 1q breakpoint, seen for certain lymphomas, 41 may lie just telomeric to Fc␥RIIIB in the low affinity Fc␥R cluster. This observation suggests a possible recombination hot spot, given the occurrence of both Fc␥RIIIB gene deletion and duplication in humans.…”

Molecular pathways in follicular lymphoma

“…110,111 Moreover, the FCGR2B gene (FcgR-IIB) also at 1q21 has been found in IgL translocations secondary to t(14;18), as well as in IgH translocations, in a small number of FLs. 112,113 Deletions at 6q11-27 are frequently found in FL and are associated with an adverse prognosis. [105][106][107] In two studies on the 6q11-27 deletions, a region of minimal deletion was identified at 6q16.3, harboring the SIM1, RNAH, DJ and GRIK genes.…”