2009 Vienna - European Society of Human Genetics

Cancer genetics
val (DFI) than patients with other IL-10 -1082, -3575 and TNF-α -308
genotypes. Also, patients with TNF-α -308GA+AA had better overall
survival (OS) (Logrank test, p=0.0371) than patients with TNF-α -
308GG.
Conclusion. Homo- and/or heterozygous carriers of high IL-10 and
TNF-α producer alleles were more susceptible to DLBCL (IL-10 -
819CC, TNF-α -308GA+AA), but they had better DFI (IL-10 -1082GG,
IL-10 -3575TT, TNF-α -308GA+AA) and OS (TNF-α -308GA+AA).
TGF-β c10TT carriers (low-producer genotype) had better prognosis
according IPI.
P06.173
Regulation of the leukemia associated oncogene and
developmental regulator EVi1 by all-trans retinoic acid (AtRA)
S. Bingemann, R. Wieser;
Department for Human Genetics, Vienna, Austria.
The EVI1 gene codes for a zinc finger protein with important roles
in embryonic development and in myeloid leukemogenesis. It is transcribed
into several mRNA species with variable 5’-ends. One of these
mRNA variants, MDS1/EVI1, gives rise to an EVI1 protein with an extended
N-terminus and with functions partially different from those of
the shorter EVI1 protein type. The other EVI1 5’-end variants are most
likely translated into the same protein, i.e. the short EVI1 protein variant,
but their variable 5’-UTRs can be expected to affect the regulation
of protein expression. So far all-trans retinoic acid (ATRA) is the only
known physiological regulator of EVI1 in mammalian cells.
Using the teratocarcinoma cell line NT-2, we have investigated the induction
of EVI1 by ATRA. Time course analyses showed that ATRA
rapidly induces the EVI1 mRNA in NT-2 cells. A maximum is reached
after approximately 48 hrs, except for the MDS1/EVI1 mRNA, which
was noticeably induced only after 48 hrs. This response was already
detectable with as little as 10 nM ATRA and affected all EVI1 mRNA
variants, albeit to variable degrees. Using reporter gene assays, an
ATRA responsive region of ~200 bp was identified within exon 1a of
EVI1. Chromatin immunoprecipitation (ChIP) experiments confirmed
the binding of retinoic acid receptors RAR and RXR to a retinoic acid
response element (RARE) in this region.
We conclude that the EVI1 gene is a direct target of retinoic acid signaling
and that its regulation via this pathway is mediated through an
intragenic RARE.
P06.174
Alterations of herg isoform expressions in pediatric acute
myeloid leukemia and solid tumors
M. Erdem 1 , T. A. Tekiner 2 , A. Fejzullahu 2 , S. Anak 3 , U. Ozbek 4 , F. Atalar 5 ;
1 Yeditepe University, Department of Genetics and Bioengineering, Istanbul,
Turkey, 2 Istanbul Technical University, Molecular Biology and Genetics Department,
Istanbul, Turkey, 3 Istanbul University, Istanbul School of Medicine,
Department of Pediatric Hematology and Oncology, Istanbul, Turkey, 4 Istanbul
University, Institute of Experimental Medical Research (DETAE), Genetics Department,
Istanbul, Turkey, 5 Istanbul University, Istanbul Medical Faculty, Child
Health Institute, Department of Pediatric Endocrinology, Istanbul, Turkey.
Expression of K + channels encoded by human ether-a-go-go related
gene(herg) is reported to be deregulated in cancer cells.We studied
the expression levels of herg1 and herg1b by qRT-PCR in 35 pediatric
acute myeloid leukemia(pAML) patients together with a group of human
tumor samples(n=40) and their healthy counterparts.A common
HERG polymorphism(K897T) was also analyzed in pAML patients.Our
results suggest that herg1 expression is lower in pAML patients compared
to the control group which is composed of CD33+ cells isolated
from healthy bone marrows(2,5fold).Herg1b expression was found
to be higher in pAML patients(20 fold,p