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Analysis of structural chromosomal rearrangements in hematological neoplasias; Study of structural chromosomal rearrangements of cells of chronic lymphocytic leukemia after DSP30/IL2 stimulated cultivation
Hrubá, Martina ; Michalová, Kyra (advisor) ; Goetz, Petr (referee) ; Březinová, Jana (referee)
Cytogenetic analysis of cells of chronic lymphocytic leukemia (CLL) is difficult because of their low proliferative activity. To obtain sufficient number of mitoses for performing chromosomal analysis a suitable stimulation of cell division is needed. Using DSP30/IL2 stimulated cultivation 391 CLL samples were investigated in 5 years' period. The cultivation was showed to have high success rate (96%; 375/391) with also high rate of detection of pathological clones by both karyotype and metaphase FISH analyses (in 84% of samples; 329/391). Almost in half of samples (44%; 171/391) other aberrations than recurrent FISH (i.e. 13q14 deletion, trisomy 12, TP53, ATM genes deletions) were found. Also high frequency of translocations (37%; 144/391), complex karyotypes (28%; 111/391) and clonal evolution, which was detected in one third of all samples (34% of samples with presence of more than two clones; 133/391) and like a new event in disease duration even more frequently (in 39% of samples repeatedly investigated after stimulated cultivation; 21/54), was revealed. The presence of translocations, complex karyotypes and clonal evolution was associated with progressive form of disease (P 0,000003, resp. P 0,0002 and P 0,05/P 0,04). In cases of the recurrent deletions the detailed analysis of metaphase...
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The serotonin transporter gene - polymorphism incidence study.
Bílá, Nikola ; Macek, Milan (advisor) ; Goetz, Petr (referee)
Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter in the central and peripheral nervous systems. Serotonin transporter 5-HTT plays an important role in serotogenic transmisssion and the serotonin transporter gene is under investigation in connection with multiple psychiatric disorders. Three polymorphisms, an insertion/deletion and SNP in the promoter region and a variable nucleotide tandem repeat (VNTR) in intron 2, influence expression of the 5-HTT gene. We examined these polymorphisms at the serotonin transporter protein locus (SLC6A4) in three specific and representative cohorts drawn from the Czech population. These cohorts were stratified according to their age: a) randomly selected elderly individuals (over 75 years of age), b) young adults (age ranging between 19- 45 years) and c) newborns, all with balanced gender representation. The two regions were amplified and resolved on a 2% agarose gel and/or analyzed using the capillary electrophoresis in order to discriminate lenght polymorphisms. SNP in intron 2 was examined by RFLP after using MspI restriction. This analysis revealed that elderly individuals were statistically more likely than controls to carry two copies of the L allele of the lenth polymorphism. This may be due to the protective character of L allele, which is associated with...
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Analysis of complex chromosomal rearrangements in tumor cells and their impact on pathogenesis and prognosis of malignant diseases
Lizcová, Libuše ; Michalová, Kyra (advisor) ; Goetz, Petr (referee) ; Kuglík, Petr (referee)
Cytogenetic abnormalities are characteristic attribute of cancer cells. To date, clonal chromosomal aberrations have been found in majority of tumors and they represent important part of management of patients with malignant diseases. Using modern molecular cytogenetic methods (I-FISH, mFISH, mBAND, CGH, aCGH, SNP array) we performed precise analysis of complex chromosomal rearrangements (CCR) in patients with various hematological malignancies and difuse gliomas. We described particular aberrations in detail and found chromosomes and chromosomal parts which were involved in CCR most frequently. We determined recurrent chromosomal breakpoints and pointed out to regions with important role in initiation and progression of the disease. From the clinical point of view, we proved that complex chromosomal aberrations found at the time of diagnosis are poor prognostic factor. In our cohorts of patients, complex chromosomal rearrangements were associated with resistance to treatment, higher occurrence of relapses and shorter overall survival. Results of our study proved significance of molecular cytogenetic analysis not only for diagnosis and prognosis of patients with different types of tumors but also for clarification of mechanisms leading to malignant transformation of the cell. Detailed chromosomal...
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