The IgG Fc receptor, FcgammaRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma.
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, FcgammaRIIB, as the target gene of the t(1;22)(q22;q11). We demonstrate deregulation of FCGR2B leading to hyperexpression of FcgammaRIIb2 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.
Callanan
M B
MB
Lymphoma Research Group, Institut Albert Bonniot, 38706 Grenoble, France.
Le Baccon
P
P
Mossuz
P
P
Duley
S
S
Bastard
C
C
Hamoudi
R
R
Dyer
M J
MJ
Klobeck
G
G
Rimokh
R
R
Sotto
J J
JJ
Leroux
D
D
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003001:Cloning, Molecular; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D012333:RNA, Messenger; D017452:Receptors, IgG