2009 Vienna - European Society of Human Genetics

Cancer genetics
genotypes were significantly associated with the increased BIL levels.
These findings will be useful for further pharmacogenomical studies on
adverse reactions to irinotecan.
P06.098
Uterine leiomyoma with high proliferative index versus
leiomyosarcoma: analyzes of allelic imbalance
A. A. Shikeeva1,2 , T. V. Kekeeva1 , L. E. Zavalishina1 , Y. Y. Andreeva1 , G. A.
Frank1 ;
1Moscow Herzen Oncological Research Institute, Moscow, Russian Federation,
2Russian State Medical University, Moscow, Russian Federation.
Uterine leiomyosarcoma (ULMS) is rare and highly malignant smooth
muscle tumor. Differential diagnosis between uterine leiomyoma with
high proliferative index (ULM) and ULMS is one of the basic problems
in pathology for nowadays. The singular morphological differential criteria
is the mitosis index (quantity of mitoses ).
We investigated allelic imbalance (AI) to find out genetic differences
between ULM and ULMS. Microsatellite analysis was evaluated by
PCR using 4 polymorphic markers for chromosomal regions 3p14,
10q22, 10q23, 10q26 in 14 patients with 23 formalin-fixed paraffin-embedded
samples (15 ULMS, 5 ULM, 3 metastatic lymphatic nodules).
10 leiomyoma specimens from patients with benign process were suggested
as control.
Our results demonstrated AI in ULMS samples with following frequencies:
D3S1295 - 5\14 (35.7%), D10S218 - 6\14 (43%), D10S541 - 6\14
(42.9%), D10S1213 - 5\14 (35.7%). Occurrence of investigated genetic
alterations (at least for the one of microsatellite markers) was revealed
in 13 leiomyosarcomas (91%). The AI frequency in ULM samples was
found only for one patient..
This research show that AI analysis may be helpful for accurate exclusion
between ULMS and ULM though further investigation is needed.
Increasing of molecular marker number will be necessary for diagnostically
challenging cases of uterine smooth muscle tumors.
P06.099
status of some tumor-suppressor loci in uveal melanoma
I. K. Manokhina 1 , N. V. Sklyarova 2 , I. P. Khoroshilova-Maslova 3 , S. V. Saakyan
2 , D. V. Zaletaev 1 ;
1 Laboratory of Human Molecular Genetics, Institute of Molecular Medicine, I.M.
Sechenov Moscow Medical Academy, Moscow, Russian Federation, 2 Ophthalmo-oncology
and radiology department, Helmholtz Moscow Research Institute
of Eye Diseases, Moscow, Russian Federation, 3 Department of Anatomical
Pathology and Histology of the Eye, Helmholtz Moscow Research Institute of
Eye Diseases, Moscow, Russian Federation.
Purpose. We investigated a panel of uveal melanomas (UM) for the
presence of allelic losses at some chromosomal regions where structural
abnormalities had previously been found, and the methylation
status of tumor suppressor genes supposed to be involved in UM
pathogenesis.
Methods. Loss of heterozygosity (LOH) at chromosomal regions 1p36,
1p31.3, 3p25.3 (VHL), 3p21.3 (RASSF1A), 3p14.2 (FHIT), 3q26.3
(TNFSF10), 9(p21.2-p21.3) (CDKN2A), 10(q23.2-q23.3) (PTEN),
13q14.2 (RB1) was investigated by PCR-based microsatellite analysis
in 107 uveal melanomas. Samples were also analyzed for the methylation
status of VHL, RASSF1A, FHIT, CDKN2A and RB1 by methylation-sensitive
restriction enzyme PCR. Clinical and histopathological
parameters were analyzed together with genetic abnormalities.
Results. Monosomy 3 was detected in 48 of 107 tumors, and showed a
significant association with the presence of epithelioid cells (P