EVI1
MIM.165215 3q26
Evi1 was characterized in the mouse as a cancer-related retroviral integration site in myeloid leukemia, and EVI1 was subsequently identified as a translocation breakpoint in humans.
The 5’ MDS part of MDS-EVI1 contains a SET domain, and both retroviral integrations in the mouse and translocations in humans result in the selective overexpression of the EVI1 variant lacking a SET domain.
EVI1 acts dominantly over its presumed antagonist MDS-EVI1, and high EVI1 expression correlates with poor prognosis in patients with acute myeloid leukemia.
Several SET domain proteins (SETs) can be found in a cancer-promoting and a cancer-preventing isoform. This is true for the RIZ and MDS-EVI1 genes, both of which contain two promoters dictating separate protein isoforms, one form holding and one form lacking the SET domain. The same picture emerges from the translocation fusion proteins involving MLL, all of which lack the SET protein domain.
In addition, cancer-specific translocations of the SET domain protein MMSET/NSD2 have been characterized, in which the SET domain is selectively lost.
Pathology
Amplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption. (#17243162#)
Involvement of EVI1 in various 3q26 rearrangements
- t(3;17)(q26;q22)
- t(2;3)(p21-22;q26)
- t(3;6)(q26;q25)
See also
3q26 rearrangement
Reviews
Mitani K. Molecular mechanisms of leukemogenesis by AML1/EVI-1. Oncogene. 2004 May 24;23(24):4263-9. PMID: #15156182#
References
Meyer S, Fergusson WD, Whetton AD, Moreira-Leite F, Pepper SD, Miller C, Saunders EK, White DJ, Will AM, Eden T, Ikeda H, Ullmann R, Tuerkmen S, Gerlach A, Klopocki E, Tonnies H. Amplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption. Genes Chromosomes Cancer. 2007 Apr;46(4):359-72. PMID: #17243162#
Poppe B, Dastugue N, Vandesompele J, Cauwelier B, De Smet B, Yigit N, De Paepe A, Cervera J, Recher C, De Mas V, Hagemeijer A, Speleman F. EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements. Genes Chromosomes Cancer. 2006 Apr;45(4):349-56. PMID: #16342172#