Kalla J, Stilgenbauer S, Schaffner C, Wolf S, Ott G, Greiner A, Rosenwald A, Döhner H, Müller-Hermelink H K, Lichter P
Organisation komplexer Genomé, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Leukemia. 2000 Nov;14(11):1967-74. doi: 10.1038/sj.leu.2401918.
The translocation t(11;18)(q21;q21), which is the most frequent chromosomal aberration in extranodal marginal zone B cell lymphomas of MALT-type, was characterised in a series of 34 biopsies, including 18 gastric non-Hodgkin's lymphomas (NHL) of MALT-type, six MALT-type NHL of extragastral origin and 10 extranodal large B cell lymphomas (LBL). Based on fluorescence in situ hybridisation, STS-PCR analysis and screening of genomic PAC libraries, a physical map of contiguous DNA probes on chromosome 11 was constructed containing the anti-apoptotic genes API2 and API1 adjacent to the translocation breakpoint. RACE-PCR experiments revealed MALT1 the chromosome 18-derived fusion partner of API2, which has also been reported recently by other groups. RT-PCR analysis and DNA sequencing demonstrated the expression of an API2-MALT1 fusion transcript in 18/24 gastral and extragastral MALT-type lymphomas. In none of 10 LBLs was a translocation specific RT-PCR product detected. Five variants of the fusion transcript were identified and in all instances the open reading frame of the fused portion of the MALT1 gene was maintained. The molecular analysis of these variants allowed the design of optimised assays for the diagnosis of the API2-MALT1 gene rearrangement.
t(11;18)(q21;q21)易位是黏膜相关淋巴组织（MALT）型结外边缘区B细胞淋巴瘤中最常见的染色体畸变。在34例活检样本中对其进行了特征分析，其中包括18例胃MALT型非霍奇金淋巴瘤（NHL）、6例胃外起源的MALT型NHL以及10例结外大B细胞淋巴瘤（LBL）。基于荧光原位杂交、STS-PCR分析以及基因组PAC文库筛选，构建了11号染色体上包含抗凋亡基因API2和API1的连续DNA探针物理图谱，这些基因与易位断点相邻。RACE-PCR实验揭示了MALT1是API2在18号染色体上的融合伴侣，其他研究组最近也报道了这一结果。RT-PCR分析和DNA测序表明，在18/24例胃和胃外MALT型淋巴瘤中存在API2-MALT1融合转录本表达。在10例LBL中均未检测到易位特异性RT-PCR产物。鉴定出了融合转录本的5种变体，并且在所有情况下MALT1基因融合部分的开放阅读框均得以保留。对这些变体的分子分析有助于设计优化的检测方法以诊断API2-MALT1基因重排。
