Galiègue-Zouitina S, Collyn-d'Hooghe M, Denis C, Mainardi A, Hildebrand M P, Tilly H, Bastard C, Kerckaert J P
U.124 INSERM, Institut de Recherches sur le Cancer de Lille, France.
Genes Chromosomes Cancer. 1994 Dec;11(4):246-55. doi: 10.1002/gcc.2870110407.
In B-cell malignancies, the t(11;14)(q13;q32) at the 11q13 BCL1 locus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between the BCL1 major translocation cluster (MTC) and the PRAD1 (also termed cyclin D1 or CCND1) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric to PRAD1. We report here the molecular cloning of a new t(11;14) breakpoint site, 20 kb centromeric to the MTC, from a patient with prolymphocytic leukemia. We subcloned a non-repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHO11c) relative to already identified breakpoint sites, using long- and short-range physical mapping within the BCL1 locus. Rearrangements in the BCL1 locus are associated with deregulation of the PRAD1 gene, which is often overexpressed, particularly in mantle-cell malignancies. The detectable but weak PRAD1 expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCL1 locus boundaries. We think that attention should be focused on this region centromeric to the BCL1-MTC, where the investigation of previously unidentified translocations may increase understanding of the PRAD1 gene deregulation in t(11;14) associated pathologies.
在B细胞恶性肿瘤中，位于11q13 BCL1基因座的t(11;14)(q13;q32)的特征是断点位点散布在一个100 kb的基因组区域内，该区域位于BCL1主要易位簇（MTC）和PRAD1（也称为细胞周期蛋白D1或CCND1）基因之间。最近，11q13断点区域在两侧都有所扩展，向MTC的着丝粒方向和PRAD1的端粒方向延伸。我们在此报告从一名幼淋巴细胞白血病患者中克隆到一个新的t(11;14)断点位点，该位点位于MTC着丝粒方向20 kb处。我们在断点附近亚克隆了一个非重复DNA片段，并利用BCL1基因座内的长程和短程物理图谱，将这个新的11q13探针（pHO11c）相对于已确定的断点位点进行定位。BCL1基因座的重排与PRAD1基因的失调有关，PRAD1基因常常过度表达，尤其是在套细胞恶性肿瘤中。在我们所呈现的病例中可检测到但较弱的PRAD1表达表明，这个位于MTC着丝粒方向的断点仍位于BCL1基因座边界内。我们认为应将注意力集中在BCL1-MTC着丝粒方向的这个区域，对先前未识别的易位进行研究可能会增进对t(11;14)相关病理中PRAD1基因失调的理解。
