The IgG Fc receptor, FcγRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma
The IgG Fc receptor, FcγRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma
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DOI：
10.1073/pnas.97.1.309
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发表时间：
2000-01-04
影响因子：
11.1
通讯作者：
Leroux, D
中科院分区：
文献类型：
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作者：
Callanan, MB;Le Baccon, P;Leroux, D
染色体1q21-23重排是血液系统恶性肿瘤中最常见的染色体异常之一。受这些重排影响的基因特征仍然很差。通常，1q21-23重排发生在肿瘤的演变过程中，并伴随着疾病特异性的染色体重排，如t(14；18)(Bcl2)和t(8；14)(Myc)，因此它们被认为在肿瘤进展中发挥重要作用。这种与1q21-23相关的疾病进展的发病基础目前尚不清楚。在这种情况下，我们调查了我们的滤泡性淋巴瘤系列以寻找1q21-23断裂复发的证据，并确定了三例t(14；18)(q32；q21)伴有新的平衡t(1；22)(q22；q11)的病例。对其中一个病例的细胞株(B593)中的t(1；22)进行分子克隆，并在其余两个病例中进行详细的荧光原位杂交定位，确定编码基于酪氨酸的免疫受体抑制基序的免疫受体Ig G Fc受体Fc-Gamma RIIB的FCGR2B基因是t(1；22)(q22；q11)的靶基因。我们证明了FCGR2B的解除调控导致Fc Gamma RIIb2的高表达是t(1；22)的主要结果。这一证据表明，在淋巴瘤中，免疫球蛋白Fc受体可以作为通过染色体易位来解除调控的靶点。提示FCGR2B基因表达异常可能在滤泡性淋巴瘤的发生发展中起一定作用。
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, Fc gamma RIIB, as the target gene of the t(1;22)(q22;q11). We demonstrate deregulation of FCGR2B leading to hyperexpression of Fc gamma RIIb2 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.