European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Cancer genetics
P0500. Automated FISH analysis predicts good outcome in
CML patients with Imatinib-induced remission and detects
very low level leukaemic cell population with double BCR-ABL
rearrangement.
G. Calabrese 1,2 , D. Fantasia 3 , P. Guanciali-Franchi 1 , R. DiGianfilippo 3 , E. Morizio
3 , M. Alfonsi 1 , R. DiLorenzo 4 , L. Stuppia 1,2 , G. Palka 1,3 ;
1 Genetica Medica, Chieti Scalo, Italy, 2 G. D’Annunzio Foundation, Chieti Scalo,
Italy, 3 Genetica Medica, Pescara Hospital, Pescara, Italy, 4 Hematology Dept,
Pescara Hospital, Pescara, Italy.
Seventy-six patients with CML, 69 in chronic phase, 1 in accelerate
phase, and 6 in blastic crisis, were treated with imatinib mesylate (IM).
The patients were studied for a 18-66 months follow up period using
cytogenetics and FISH analysis with a dual-fusion BCR-ABL probe,
and an automated FISH imaging system for rare cell events (BioView-
Duet). Before IM treatment 50 patients showed Ph chromosome in all
examined cells while in the remaining 26 patients a normal clone was
also found. Complete or partial cytogenetic remission rate [CCR or
PCR: t(9;22) absent or 97% (specificity of >94%). However, FISH is
labor intensive requiring a high skill level and somewhat subjective
interpretation. An automated system for FISH analysis has the potential
to reduce interpretation errors and decrease turn around times for
patient results. We report here the use of a fully-automated, robotic
fluorescence microscopy platform in the identification and analysis of
cells, in urine sediment, for the diagnosis of bladder cancer or tumor
recurrence.
100 patients suspected of having bladder cancer or bladder cancer recurrence
were analyzed in a blinded study. A single slide was prepared
from each patient’s urine then analyzed manually on a fluorescence
microscope. The slide was then loaded on the automated microscopy
platform for FISH analysis. 50 of the slides were run on a second platform
for intra-instrument comparisons.
97% of the samples showed complete concordance between the results
obtained by manual and automated analysis. 19 samples were
positive by both methods, 76 negative and 2 inconclusive. 2 samples
were negative by manual analysis and inconclusive by automated and
1 sample was negative by automated analysis and inconclusive by
manual. For the 50 slides run sequentially on two instruments, 49 gave
the same result from both analyses. One slide was read as normal on
the first instrument and inconclusive when run a second time, probably
due to deterioration of the FISH signals.
These data suggest that an automated FISH analysis system is capable
of providing accurate detection and enumeration of FISH signals
in voided urine samples and has the potential to increase efficiency in
the detection of bladder cancer and tumor recurrence.
P0503. Polymorphism of DNA repair genes XRCC1 and risk of
brain tumors
S. L. Cengiz 1,2 , H. Acar 1,3 , Z. Inan 1,3 ;
1 Selcuk University, Konya, Turkey, 2 Selcuk University , Meram Medicine Faculty,
Neurosurgery Department, Konya, Turkey, 3 Selcuk University , Meram Medicine
Faculty, Genetics Department, Konya, Turkey.
Background and Objective: DNA repair genes play a major role in maintaining
genomic stability through different repair pathways. The current
study was designed to evaluate the relation between polymorphism of
DNA repair gene XRCC1 and brain tumours. Their frequencies were
also compared with patient‘s age, gender, smoking, alcohol status,
family history, and tumor histopathology in a Turkish population.
Methods: We conducted a case-population base study including 135
cases of brain tumors and 87 population base age- and sex-matched
healthy controls to examine the role of polymorphism of XRCC1 Arg-
399Gln gene, in the context of brain tumor risk for the Turkish population.
Tumors were subdivided into 4 main groups that constitute 85%
of brain tumors, according to tumor histopathological examination..
Group I; patients with glial tumors (n=71), Group II; patients with meningiomas
(n=35), Group III; patients with pituitary adenomas (n=21)
and Group IV; patients with metastases to the brain (n=8).
Results: There was no significant difference in the distributions of
XRCC1 Arg399Gln polymorphisms among the gliomas, meningiomas
and the controls. However XRCC1 Arg399Gln, polymorphism were
significantly different in pituitary adenomas and metastases to brain.
As metastases to brain were compared with primary brain tumors the
difference was also significant.
Conclusion: These results suggest that the XRCC1 Arg399Gln polymorphism
may be a marker for the susceptibility to pituitary adenomas
and metastases to brain.
Key Words: brain tumors, DNA repair gene, genetics, polymorphism,
XRCC1
P0504. The role of XPD gene polymorphism in brain tumors
S. L. Cengiz1,2 , Z. Inan1,3 , T. Cora1,4 , H. Acar1,5 , S. Yavuz1,6 , A. Baysefer1,6 ;
1 2 Selcuk University, Konya, Turkey, Selcuk University, Meram Medicine
Faculty,Neurosurgery Department, Konya, Turkey, 3Selcuk University,Meram
Medicine faculty,Genetics Department, Konya, Turkey, 4selcuk University,
Meram medicine Faculty,Genetics Department, Konya, Turkey, 5Selcuk University,Meram Medicine Faculty,Genetics Department, Konya, Turkey,
6Selcuk University,Meram Medicine Faculty,Neurosurgery Department, Konya,
Turkey.
Background and Objective: Deficits in DNA repair pathways may lead
to tumorigenesis and pathogen defence. The current study was designed
to evaluate the relation between polymorphism of DNA repair
gene xeroderma pigmentosum group D (XPD) and brain tumors. We
aimed to investigate it’s role as susceptibility marker for brain tumors.
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