EVII is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements

Abstract

In contrast to the well-documented involvement of EVII in various 3q26 aberrations, the transcriptional status of EVII 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 EVII expression was questioned. Therefore, we performed a detailed physical mapping of 3q26 breakpoints using a 1.3-Mb tiling path BAC contig covering the EVII locus and a carefully designed quantification of both EVII and MDS/EVII 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 EVII rearrangements on both metaphases and interphase nuclei. Real-time quantitative PCR analyses indicated that typically both MDSI/EVII and EVII, but not MDSI, were expressed in these malignancies, with EVII the primary transcript. In conclusion, we have demonstrated EVII 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 EVII deranged leukemias and identified EVII as the principal transcript expressed in these malignancies. © 2005 Wiley-Liss, Inc.