Poppe Bruce, Dastugue Nicole, Vandesompele Jo, Cauwelier Barbara, De Smet Betty, Yigit Nurten, De Paepe Anne, Cervera Jose, Recher Christian, De Mas Véronique, Hagemeijer Anne, Speleman Frank
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Genes Chromosomes Cancer. 2006 Apr;45(4):349-56. doi: 10.1002/gcc.20295.
In contrast to the well-documented involvement of EVI1 in various 3q26 aberrations, the transcriptional status of EVI1 in rare recurrent or sporadic 3q26 chromosomal defects has remained largely unexplored. Moreover, in a recent report, the association between 3q26 alterations in myeloid proliferations and ectopic EVI1 expression was questioned. Therefore, we performed a detailed physical mapping of 3q26 breakpoints using a 1.3-Mb tiling path BAC contig covering the EVI1 locus and a carefully designed quantification of both EVI1 and MDS/EVI1 transcripts in 30 hematological malignancies displaying 3q26 aberrations. Cases included well-known rare, recurring chromosomal aberrations such as t(3;17)(q26;q22), t(2;3)(p21-22;q26), and t(3;6)(q26;q25), as well as 10 new sporadic cases. Extensive 3q26 breakpoint mapping allowed unequivocal and sensitive FISH detection of EVI1 rearrangements on both metaphases and interphase nuclei. Real-time quantitative PCR analyses indicated that typically both MDS1/EVI1 and EVI1, but not MDS1, were expressed in these malignancies, with EVI1 the primary transcript. In conclusion, we have demonstrated EVI1 involvement in numerous novel sporadic and recurrent 3q26 rearrangements. Our results underscore the feasibility of FISH as an adjunct to PCR for the identification of EVI1 deranged leukemias and identified EVI1 as the principal transcript expressed in these malignancies.
与EVI1在各种3q26畸变中的明确作用相反，EVI1在罕见的复发性或散发性3q26染色体缺陷中的转录状态在很大程度上仍未得到探索。此外，在最近的一份报告中，骨髓增殖中3q26改变与异位EVI1表达之间的关联受到质疑。因此，我们使用覆盖EVI1基因座的1.3-Mb平铺路径BAC重叠群对3q26断点进行了详细的物理定位，并对30例显示3q26畸变的血液系统恶性肿瘤中的EVI1和MDS/EVI1转录本进行了精心设计的定量分析。病例包括众所周知的罕见复发性染色体畸变，如t(3;17)(q26;q22)、t(2;3)(p21-22;q26)和t(3;6)(q26;q25)，以及10例新的散发性病例。广泛的3q26断点定位使得能够在中期和间期核上明确且灵敏地通过FISH检测EVI1重排。实时定量PCR分析表明，在这些恶性肿瘤中通常MDS1/EVI1和EVI1均有表达，但MDS1无表达，其中EVI1是主要转录本。总之，我们证明了EVI1参与了众多新的散发性和复发性3q26重排。我们的结果强调了FISH作为PCR辅助手段用于鉴定EVI1紊乱白血病的可行性，并确定EVI1是这些恶性肿瘤中表达的主要转录本。
