Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A
Department of Pathology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Leukemia. 2005 Apr;19(4):652-8. doi: 10.1038/sj.leu.2403644.
The three chromosomal translocations t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32) are associated with MALT lymphoma. In a case of MALT lymphoma of the thyroid, we observed t(3;14)(p14.1;q32) by cytogenetic analysis. Fluorescence in situ hybridization studies showed that the immunoglobulin heavy chain locus (IGH) was rearranged on chromosome 14. Long-distance inverse polymerase chain reaction identified FOXP1 as the partner gene on chromosome 3. To determine the frequency of the t(3;14)(p14.1;q32), two fluorescence in situ hybridization assays were established to screen 91 MALT lymphomas, all of which were negative for the above-mentioned three translocations, and eight splenic and six nodal marginal zone lymphomas. Overall, nine MALT lymphomas (10%) harbored t(3;14)(p14.1;q32) comprising tumors of the thyroid (three of six), ocular adnexa (four of 20), and skin (two of 20), whereas those of the stomach (n = 20), salivary gland (n = 20), and lung (n = 5) were negative as well as the splenic and nodal marginal zone lymphomas. Most t(3;14)(p14.1;q32) + MALT lymphomas harbored additional genetic abnormalities, such as trisomy 3. Further studies revealed that the three known translocations and t(3;14)(p14.1;q32) are mutually exclusive. Real-time quantitative reverse transcriptase polymerase chain reaction showed upregulation of FOXP1 in cases with t(3;14)(p14.1;q32) or trisomy 3. This study identifies FOXP1 as a new translocation partner of IGH in a site-dependent subset of MALT lymphomas.
三种染色体易位,即t(11;18)(q21;q21)、t(14;18)(q32;q21)和t(1;14)(p22;q32)与黏膜相关淋巴组织(MALT)淋巴瘤相关。在1例甲状腺MALT淋巴瘤中,我们通过细胞遗传学分析观察到t(3;14)(p14.1;q32)。荧光原位杂交研究显示免疫球蛋白重链基因座(IGH)在14号染色体上发生重排。长距离反向聚合酶链反应确定FOXP1为3号染色体上的伙伴基因。为了确定t(3;14)(p14.1;q32)的频率,建立了两种荧光原位杂交检测方法,用于筛查91例MALT淋巴瘤(所有这些病例均未出现上述三种易位)、8例脾边缘区淋巴瘤和6例结边缘区淋巴瘤。总体而言,9例MALT淋巴瘤(10%)存在t(3;14)(p14.1;q32),包括甲状腺肿瘤(6例中的3例)、眼附属器肿瘤(20例中的4例)和皮肤肿瘤(20例中的2例),而胃(n = 20)、唾液腺(n = 20)和肺(n = 5)的肿瘤以及脾和结边缘区淋巴瘤均为阴性。大多数t(3;14)(p14.1;q32)阳性的MALT淋巴瘤还存在其他基因异常,如3号染色体三体。进一步研究表明,三种已知的易位和t(3;14)(p14.1;q32)相互排斥。实时定量逆转录聚合酶链反应显示,在存在t(3;14)(p14.1;q32)或3号染色体三体的病例中FOXP1表达上调。本研究确定FOXP1是MALT淋巴瘤一个位点依赖性亚组中IGH的新易位伙伴。
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