title: EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements.
abstract: 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.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Barbara
authors.initials: B
authors.lastname: Cauwelier
authors.forename: Betty
authors.initials: B
authors.lastname: De Smet
authors.forename: Nurten
authors.initials: N
authors.lastname: Yigit
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Jose
authors.initials: J
authors.lastname: Cervera
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.forename: Véronique
authors.initials: V
authors.lastname: De Mas
authors.forename: Anne
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D020161:Physical Chromosome Mapping; D011519:Proto-Oncogenes / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors