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

Cancer genetics
P0532. Secondary chromosomal abnormalities within
Philadelphia positive Chronic Myeloid Leukemia
B. Saglam, K. Yararbas, I. Akalın, H. Ilgın Ruhi, T. Tuncali, H. G. Karabulut, N.
Yurur Kutlay, A. Vicdan, F. Sadeghi, A. Tukun;
Ankara University Faculty of Medicine Department of Medical Genetics, Ankara,
Turkey.
Chronic myeloid leukemia (CML) is a stem cell disorder characterized
by Philadelphia chromosome (Ph), showing a progression into
an agressive blast phase from a chronic phase. This progression is
frequently preceeded by secondary chromosomal abnormalities which
are considered as the cytogenetic signs of progression. In this respect
a retrospective analysis of 162 cases of CML with Ph was performed
in our department. In 43 of the cases, presence of extra chromosomal
abnormalities was observed. The most frequent abnormalities were +8
(7 cases); -20, -21, -Y (4 cases each); -5, -7, -12, -13, del(17)(q25)(3
cases each); and -18, -19, i(17)(q10), del(17)(p13)(2 cases each). 28
different rearrangements such as t(2;8)(p21;q24), inv(4)(p14;q12),
t(3;4)(q13;q31) not previously associated with Ph+ CML were observed.
The cumulative data on cytogenetic studies of Ph+ CML will
contribute not only to the prediction of the prognosis but also to the
enhancement of monitoring responses to the treatment.
P0533. A unique complex translocations (9;22;6) in a patient with
chronic myelogenous leukemia
M. Khaleghian, C. Azimi;
Cancer Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic
of Iran.
Complex chromosome translocations involve changes between three
or more chromosomes and are found very rarely in the general population.
Chronic myelogenous leukemia (CML) is characterized in about 90-
95% of cases by a karyotypic marker, the Philadelphia chromosome,
originating from a reciprocal translocation of chromosomes 9 and 22,
t(9;22)(q34;q11), and genetically resulting in the fusion of BCR/ABL
gene. About 5-10% of Philadelphia positive patients with CML show
various complex translocations involving the third chromosome in addition
to chromosomes 9 and 22.
In this study we report a 20-year-old male patient with a diagnosis of
CML with unusual and complex translocations involving chromosomes
9, 22 and 6.
Cytogenetic analysis was done on a 24-hour culture of bone marrow
specimen. The cells were cultured by conventional methods and processed
by standard techniques, using GTG-banding. The FISH were
performed according to the manufacturers’ directions, using whole
chromosome painting probes.
The karyotype of our case was: t(9;22;6)(q34;q11;p21).
Apparently, the first translocation occurred between chromosomes 9q
and 22q resulting to the formation of Philadelphia chromosome. Then
the distal segment of the chromosome 6p has been translocated to the
end of the derivative chromosome 9.
According to literature review and to the best of our knowledge, our
case is a unique tranlocations which has not been reported.
P0534. Correlation between p53 protein accumulation and the
development of colon cancer from Iran
N. Taghavi1 , F. Biramijamal1 , G. Iravanloo2 , K. Shamimi3 , P. Azimi4 , M. Soltani1 ,
E. Nazari1 ;
1National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran,
Islamic Republic of Iran, 2Cancer Institute, Tehran, Islamic Republic of Iran,
3University of Medical Sciences-Dept. Surgery, Tehran, Islamic Republic of Iran,
4University of Medical Sciences-Dept. Pathology, Tehran, Islamic Republic of
Iran.
Colorectal cancer is the third cause of the cancer-related death in the
world and the fourth most common cancer in Iran. The peak age is between
60-80 years old, while about 20% of cases occur under the age
of 50. It is estimated that the annual incidence rate of colorectal cancer
is about 150,000 and the death toll is 50,000 around the world. One
of the basic mutation involved in these tumors include inactivation or
alteration of p53 gene. Changes in this tumor suppressor gene are the
basic event in many cancers. One of the methods to identify changes
in this gene includes Immunohistochemistry (IHC). We studied the expression
of p53 protein in cancerous and normal tissues from colon
cancer patients for predicting the natural path of the disease and also
developing cancerous cells in tissue.
In order to evaluate the highest risk patients, p53 nuclear accumulation
evaluated by monoclonal antibody DO7 and Envision + Dual link+DAB
(kit) in ordinary paraffin-embedded tissue sections. The method used
to assess p53 status were immunohistochemistry (IHC), indicating accumulation
of p53 in tumoral and normal tissue in colorectal cancer
patients. P53 protein accumulation was seen in tumor tissues and normal
cells adjacent to tumor cells. Our finding suggested that detection
of p53 protein accumulation may play an important role in developing
colon cancerous cells among cancer patients. It is suggested that detection
of the p53 gene mutation can be investigate among colon cancerous
cells and normal tissue adjacent to tumor cells in the future.
P0535. No association between the CHEK2 I157T allelic variant
and colorectal cancer in Bulgaria
T. K. Kadiyska 1 , D. V. Konstantinova 1 , V. B. Sokolova 1 , M. B. Mirchev 2 , R. P.
Kaneva 1 , I. M. Kremensky 1 , V. I. Mitev 3 ;
1 Laboratory of Molecular Pathology, Sofia, Bulgaria, 2 University Hospital “St.
Marina”, Varna, Bulgaria, 3 Department of Chemistry and Biochemistry, Medical
University, Sofia, Bulgaria.
In the development of colorectal cancer (CRC), genetic and environmental
factors are involved, but the exact mechanism of carcinogenesis
still remains unclear. The CHEK2 gene encodes a protein kinase
that participates in the DNA damage response in many cell types.
Three founder alleles have been described in this gene and all of them
were associated with different cancer types.
The missense variant c.470 T>C, p. I157T has been associated with
an increased risk of breast, colon, kidney, prostate, and thyroid cancer.
This variant was also seen in healthy population controls.
Aim: To determine the frequency of the I157T alleles in Bulgarian patients
with CRC and healthy controls.
Methods: The analysis was performed in a total of 299 patients and
273 healthy individuals. Samples were analyzed by PCR- RFLP. All
mutations were further confirmed by direct sequencing.
Results: The I157T variant was found in 8 patients (2,7%) and 8 controls
(2,9%). There was no association between the mutation and
CRC. The patient group was then divided according to family history
and each of them was compared to controls and in between, but again
no significant differences were found in their frequencies. Different
extra-colonic tumors were described in the pedigrees of three family
cases. Conclusions: Our results from this case - control study do not
confirm the role of the I157T mutation in the development of CRC in
the Bulgarian population. Larger studies are required to investigate
the tendency for higher frequency of different cancer types in mutation
carriers.
P0536. Pattern of distribution of SNPs in DNA repair genes in
colorectal cancer patients - a preliminary report.
J. Gil1 , P. Karpinski1 , P. Leszczynski1 , I. Laczmanska1 , D. Ramsey2 ;
1 2 Department of Genetics, Wroclaw, Poland, School of Mathematics and Statistics,
Limerick, Ireland.
Epidemiological data shows that colorectal cancer (CRC) is the second
most frequent cancer. One to two percent of all CRCs are caused by
mutation in APC which leads to familial adenomatuos polyposis while
about 5-10% of all CCR is caused by mutations in mismatch repair
genes leading to hereditary non-polyposis colorectal cancer (HNPCC)
syndrome. Although the participation of the mentioned above mutations
in CRC development is obvious, in more than 85% of cases the
genetic background remains unknown.
The involvement of “minor impact genes” such as XME and DNA-repair
genes in aetiology of sporadic cancer is postulated by other authors
therefore in our research we focused on analysis of polymorphisms
in DNA-repair genes in CRC. On the basis of the recently published
studies we hypothesise that it is not a single genetic alteration but a
network of polymorphisms that plays a key role in the individual susceptibility
to cancer. In order to verify this hypothesis we have chosen
11 genes involved in three different ways of DNA repair: base excision
repair (BER- OGG1, XRCC1), nucleotide excision repair (NER- XPA,
XPC, XPD, XPG, XPF, ERCC1) and homologous recombination repair
(HR-RAD51, XRCC3, NBS1). The study group consists of 133 patients
with CRC; 20 of them diagnosed with HNPCC or suspected of HNPCC
and the rest with sporadic cancer.
We compare the frequency of polymorphisms between patients’ and
1