2008 Barcelona - European Society of Human Genetics

Cancer genetics
gene) protein is a clathrin assembly protein which plays a role in clathrin-mediated
endocytosis and trans Golgi network trafficking. AF10
is a putative transcription factor likely involved in processes related to
chromatin organization .
To learn about the function of CALM/AF10 fusion protein, we searched
for protein interaction partners of CALM using a yeast-two-hybrid assay
and identified FHL2 as a putative CALM interacting partner. The
CALM-FHL2 interaction was confirmed by GST pull-down and CoIP
experiments . In co-localization studies a translocation from cytoplasm
to the nucleus is seen .
Expression analysis (Affymetrix based) in CML and different AML subtypes
showed a significantly higher expression of FHL2 in CML and
AML with complex aberrant karyotypes compared to AML with normal
karyotypes or balanced chromosomal translocations like the t(8;21),
inv(16) or t(15;17) .
Reporter gene assays using a GAL4-DNA binding domain FHL2 fusion
protein and a GAL4 responsive luciferase reporter were able
to demonstrate a transcriptional activation function of FHL2 that got
inhibited when adding CALM but not CALM/AF10. Previous findings
show that high expression of FHL2 in breast cancer associate with an
adverse prognosis .
It is thus conceivable that CALM/AF10 may play a role in a pathway
that enforces progression of malignancy when not downregulating the
FHL2 expression .
P04.086
Polymorphisms and haplotypes of the NBs1 gene in childhood
acute lekemia
M. Mosor1 , I. Ziolkowska1 , D. Januszkiewicz-Lewandowska1,2 , J. Nowak1 ;
1 2 Polish Academy of Sciences, Poznań, Poland, University of Medical Science,
Poznań, Poland.
DNA repair gene polymorphisms and mutations may influence cancer
risk . The product of NBS1 gene, nibrin, is functionally involved in
double strand DNA break repair system . Heterozygous, germline mutations
of the NBS1 gene are associated with increased risk of tumors
including familial/sporadic breast and prostate cancer, larynx cancer
and childhood acute lymphoblastic leukemia . So far reports on NBS1
polymorphisms in lymphoproliferative diseases are scare . The aim
of the present study was to answer the question whether polymorphisms
of NBS1 gene may influence susceptibility to the development
of childhood acute leukemia . We genotyped c .102G>A, c .553G>C,
c .1124+18C>T, c .1197T>C c .2016A>G c .2071-30A>T polymorphisms
of the NBS1 gene in 157 cases of childhood acute leukemia and 275
control subjects . . The distribution of allele, genotype and haplotype
of the polymorphisms were compared between cases and controls
using PCR-SSCP and Chi-square test . The TT genotype of c .2071-
30A>T polymorphism was increased in leukemia patients than in
healthy controls ((p=0.04), OR=1.828 (1.005 to 3.325)). No significant
differences in allele and genotypes frequencies at the other five polymorphisms
sites were observed in a comparison of leukemia cases
and controls . Genotyping data from six polymorphisms loci in NBS1 in
leukemia cases and controls, were used to impute haplotypes . Three
main haplotypes made up the majority of cases and controls (GGC-
TAA (41%), ACTCGT (20%), GGCCAA (11%)) . Two of them GGCTAA
and ACTCGT were associated with significantly increased leukemia
risk, p=0 .0038 and p