Molecular evolution of ets genes from avians to mammals and their cytogenetic localization to regions involved in leukemia.
The mammalian homologues of the ets-region from the transforming gene of avian erythroblastosis virus, E26, consists of two distinct domains located on different chromosomes. Using somatic cell hybrid panels, the mammalian homolog of the 5' v-ets-domain (ets-1) was mapped to chromosome 11 in man, to chromosome 9 in mouse, and to chromosome D1 in cat. The mammalian homolog of the 3' v-ets domain (ets-2) was similarly mapped to human chromosome 21, to mouse chromosome 16, and to feline chromosome C2. To better define the human proto-ets domains, the genomic DNA was molecularly cloned and sequences analyzed. The ets-related sequences of human DNA on chromosomes 11 and 21 were found to be discontiguous, unlike that of the chicken and avian E26 virus genome, except for a small overlap region. We conclude that the ets sequence shared by the virus, the chicken and man is likely to contain at least two dissociable functional domains, identifiable as ets-1 and ets-2. The human ets-1 locus is transcriptionally active and encodes a single mRNA of 6.8 kb, while the second locus, human ets-2 encodes three mRNAs of 4.7, 3.2 and 2.7 kb. By contrast, the chicken homolog, having a contiguous ets-1 and ets-2 sequence, is primarily expressed in normal chicken cells as a single 7.5 kb mRNA. Because chromosome translocations have been associated with different human disorders, we have used our human probes with two panels of rodent-human cell hybrids to study specific translocations occurring in acute myeloid leukemias (AML). The human ets-1 gene was found to translocate from chromosome 11 to 4 in t(4;11)(q21;q23) and the human ets-2 gene was found to translocate from chromosome 21 to 8 in t(8;21)(q22;q22). Both translocations were found associated with the altered expression of ets.
Papas
T S
TS
Division of Cancer Etiology, National Cancer Institute, Frederick, MD 21701.
Watson
D K
DK
Sacchi
N
N
O'Brien
S J
SJ
Ascione
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002415:Cats; D002645:Chickens; D002874:Chromosome Mapping; D004247:DNA; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011519:Proto-Oncogenes; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic
D004247:DNA