13 results on '"Kantorova, B."'
Search Results
2. Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia
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Malcikova, J, Stano-Kozubik, K, Tichy, B, Kantorova, B, Pavlova, S, Tom, N, Radova, L, Smardova, J, Pardy, F, Doubek, M, Brychtova, Y, Mraz, M, Plevova, K, Diviskova, E, Oltova, A, Mayer, J, Pospisilova, S, and Trbusek, M
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- 2015
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3. Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status
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Kubesova, B, primary, Pavlova, S, additional, Malcikova, J, additional, Kabathova, J, additional, Radova, L, additional, Tom, N, additional, Tichy, B, additional, Plevova, K, additional, Kantorova, B, additional, Fiedorova, K, additional, Slavikova, M, additional, Bystry, V, additional, Kissova, J, additional, Gisslinger, B, additional, Gisslinger, H, additional, Penka, M, additional, Mayer, J, additional, Kralovics, R, additional, Pospisilova, S, additional, and Doubek, M, additional
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- 2017
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4. Recurrent mutations refine prognosis in chronic lymphocytic leukemia
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Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, Rosenquist, Richard, Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, and Rosenquist, Richard
- Abstract
Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods., De tre sista författarna delar sistaförfattarskapet.
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- 2015
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5. Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia
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Malcikova, J, primary, Stano-Kozubik, K, additional, Tichy, B, additional, Kantorova, B, additional, Pavlova, S, additional, Tom, N, additional, Radova, L, additional, Smardova, J, additional, Pardy, F, additional, Doubek, M, additional, Brychtova, Y, additional, Mraz, M, additional, Plevova, K, additional, Diviskova, E, additional, Oltova, A, additional, Mayer, J, additional, Pospisilova, S, additional, and Trbusek, M, additional
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- 2014
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6. Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status
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Kubesova, B, Pavlova, S, Malcikova, J, Kabathova, J, Radova, L, Tom, N, Tichy, B, Plevova, K, Kantorova, B, Fiedorova, K, Slavikova, M, Bystry, V, Kissova, J, Gisslinger, B, Gisslinger, H, Penka, M, Mayer, J, Kralovics, R, Pospisilova, S, and Doubek, M
- Abstract
The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2–16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression.
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- 2018
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7. DECREASED EXPRESSION OF WNT3, A CANONICAL WNT PATHWAY LIGAND, IS FREQUENT IN CHRONIC LYMPHOCYTIC LEUKEMIA PROGRESSION AND IDENTIFIES PATIENTS WITH SHORT TREATMENT-FREE SURVIVAL IN MUTATED IGHV SUBSET
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Poppova, L., Janovska, P., Plevova, K., Radova, L., Plesingerova, H., Borsky, M., Kotaskova, J., Kantorova, B., Hlozkova, M., Figulova, J., Brychtova, Y., Doubek, M., Kozubik, A., Pospisilova, S., Sarka Pavlova, and Bryja, V.
8. Recurrent mutations refine prognosis in chronic lymphocytic leukemia
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Kostas Stamatopoulos, Achilles Anagnostopoulos, Karin E. Smedby, Diego Cortese, Neus Villamor, Alba Navarro, C. Belessi, La. Sutton, E. Minga, Larry Mansouri, Gianluca Gaidano, Eugen Tausch, Paolo Ghia, Richard Rosenquist, Veronika Navrkalová, Šárka Pospíšilová, Jana Kminkova, Julio Delgado, Anastasia Hadzidimitriou, Lydia Scarfò, Gunnar Juliusson, Andreas Agathangelidis, Davide Rossi, Jonathan C. Strefford, Zadie Davis, Antonios M. Makris, Matthew J. J. Rose-Zerilli, David Oscier, Stephan Stilgenbauer, Panagiotis Baliakas, Elias Campo, Barbara Kantorová, Marta Larrayoz, Evangelia Stalika, Baliakas, P., Hadzidimitriou, A., Sutton, L. -A., Rossi, D., Minga, E., Villamor, N., Larrayoz, M., Kminkova, J., Agathangelidis, A., Davis, Z., Tausch, E., Stalika, E., Kantorova, B., Mansouri, L., Scarfo', L., Cortese, D., Navrkalova, V., Rose-Zerilli, M. J. J., Smedby, K. E., Juliusson, G., Anagnostopoulos, A., Makris, A. M., Navarro, A., Delgado, J., Oscier, D., Belessi, C., Stilgenbauer, S., Ghia, P., Pospisilova, S., Gaidano, G., Campo, E., Strefford, J. C., Stamatopoulos, K., and Rosenquist, R.
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Oncology ,Male ,Cancer Research ,Time Factors ,Chronic lymphocytic leukemia ,DNA Mutational Analysis ,medicine.disease_cause ,0302 clinical medicine ,Recurrence ,hemic and lymphatic diseases ,Receptor, Notch1 ,0303 health sciences ,Mutation ,Hematology ,Middle Aged ,Prognosis ,3. Good health ,Europe ,Leukemia ,030220 oncology & carcinogenesis ,Female ,RNA Splicing Factors ,IGHV@ ,medicine.medical_specialty ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Cytogenetics ,Internal medicine ,medicine ,Humans ,Clinical significance ,neoplasms ,030304 developmental biology ,Aged ,business.industry ,Ribonucleoprotein, U2 Small Nuclear ,medicine.disease ,Phosphoproteins ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphoma ,Immunology ,Multivariate Analysis ,Tumor Suppressor Protein p53 ,business ,Trisomy ,Gene Deletion - Abstract
Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P
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- 2014
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9. Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia.
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Plevova P, Tvrda P, Paprskarova M, Turska P, Kantorova B, Mrazkova E, and Zapletalova J
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- Actins genetics, Adolescent, Adult, Child, Child, Preschool, Connexin 26, Czech Republic, DNA Mutational Analysis methods, Extracellular Matrix Proteins genetics, Female, Humans, Infant, KCNQ Potassium Channels genetics, Male, Membrane Proteins genetics, Microfilament Proteins genetics, Middle Aged, Serpins genetics, Young Adult, Connexins genetics, Deafness genetics, Hearing Loss, Sensorineural genetics, Mutation genetics
- Abstract
Background and Objective: Hearing loss is the most common sensory deficit in humans. The aim of this study was to clarify the genetic aetiology of nonsyndromic hearing loss in the Moravian-Silesian population of the Czech Republic., Patients and Methods: This study included 200 patients (93 males, 107 females, mean age 16.9 years, ranging from 4 months to 62 years) with nonsyndromic sensorineural hearing loss. We screened all patients for mutations in GJB2 and the large deletion del( GJB6 -D13S1830). We performed further screening for additional genes ( SERPINB6 , TMIE , COCH , ESPN , ACTG1 , KCNQ4 , and GJB3 ) with Sanger sequencing on a subset of patients that were negative for GJB2 mutations., Results: We detected biallelic GJB2 mutations in 44 patients (22%). Among these patients, 63.6%, 9.1% and 2.3% exhibited homozygous c.35delG, p.Trp24*, and p.Met34Thr mutations, respectively. The remaining 25% of these patients exhibited compound heterozygous c.35delG, c.-23+1G>A, p.Trp24*, p.Val37Ile, p.Met34Thr, p.Leu90Pro, c.235delC, c.313_326del14, p.Ser139Asn, and p.Gly147Leu mutations. We found a monoallelic GJB2 mutation in 12 patients (6.6%). We found no pathogenic mutations in the other tested genes. Conclusions: One fifth of our cohort had deafness related to GJB2 mutations. The del( GJB6 -D13S1830), SERPINB6 , TMIE , COCH , ESPN , ACTG1 , GJB3 , and KCNQ4 mutations were infrequently associated with deafness in the Moravian-Silesian population. Therefore, we suggest that del( GJB6 -D13S1830) testing should be performed only when patients with deafness carry the monoallelic GJB2 mutation.
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- 2018
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10. Single cell analysis revealed a coexistence of NOTCH1 and TP53 mutations within the same cancer cells in chronic lymphocytic leukaemia patients.
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Kantorova B, Malcikova J, Brazdilova K, Borsky M, Plevova K, Smardova J, Radova L, Tom N, Trbusek M, Diviskova E, Francova HS, Navrkalova V, Doubek M, Brychtova Y, Mayer J, and Pospisilova S
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- Alleles, Clonal Evolution genetics, DNA Mutational Analysis methods, Genotype, Humans, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Single-Cell Analysis methods, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Receptor, Notch1 genetics, Tumor Suppressor Protein p53 genetics
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- 2017
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11. Fragment analysis represents a suitable approach for the detection of hotspot c.7541_7542delCT NOTCH1 mutation in chronic lymphocytic leukemia.
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Vavrova E, Kantorova B, Vonkova B, Kabathova J, Skuhrova-Francova H, Diviskova E, Letocha O, Kotaskova J, Brychtova Y, Doubek M, Mayer J, and Pospisilova S
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- High-Throughput Nucleotide Sequencing, Humans, DNA Mutational Analysis methods, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation, Peptide Fragments analysis, Receptor, Notch1 genetics
- Abstract
The hotspot c.7541_7542delCT NOTCH1 mutation has been proven to have a negative clinical impact in chronic lymphocytic leukemia (CLL). However, an optimal method for its detection has not yet been specified. The aim of our study was to examine the presence of the NOTCH1 mutation in CLL using three commonly used molecular methods. Sanger sequencing, fragment analysis and allele-specific PCR were compared in the detection of the c.7541_7542delCT NOTCH1 mutation in 201 CLL patients. In 7 patients with inconclusive mutational analysis results, the presence of the NOTCH1 mutation was also confirmed using ultra-deep next generation sequencing. The NOTCH1 mutation was detected in 15% (30/201) of examined patients. Only fragment analysis was able to identify all 30 NOTCH1-mutated patients. Sanger sequencing and allele-specific PCR showed a lower detection efficiency, determining 93% (28/30) and 80% (24/30) of the present NOTCH1 mutations, respectively. Considering these three most commonly used methodologies for c.7541_7542delCT NOTCH1 mutation screening in CLL, we defined fragment analysis as the most suitable approach for detecting the hotspot NOTCH1 mutation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
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- 2017
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12. Decreased WNT3 expression in chronic lymphocytic leukaemia is a hallmark of disease progression and identifies patients with worse prognosis in the subgroup with mutated IGHV.
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Poppova L, Janovska P, Plevova K, Radova L, Plesingerova H, Borsky M, Kotaskova J, Kantorova B, Hlozkova M, Figulova J, Brychtova Y, Machalova M, Urik M, Doubek M, Kozubik A, Pospisilova S, Pavlova S, and Bryja V
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- Cell Communication, Cell Line, Cohort Studies, Disease Progression, Female, Genes, Immunoglobulin Heavy Chain genetics, Humans, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Mutation, Prognosis, Wnt Signaling Pathway, Gene Expression Regulation, Neoplastic, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Wnt3 Protein genetics
- Abstract
The canonical Wnt pathway, dependent on β-catenin-controlled transcription, is the most explored Wnt pathway, known to drive the malignant transformation of multiple cell types. Several reports have suggested that this pathway also participates in chronic lymphocytic leukaemia (CLL) pathogenesis. To get a better insight into the role of the Wnt/β-catenin pathway in CLL we analysed in detail the expression of the most overexpressed Wnt ligand, encoded by the WNT3 gene, in a well-defined cohort of 137 CLL patients. Our analysis demonstrated that (i) untreated patients with more aggressive disease (with a notable exception of patients with 11q deletion) express less WNT3, (ii) WNT3 declines with disease progression in a significant proportion of patients and (iii) low WNT3 was identified as a strong independent marker indicating shorter treatment-free survival in CLL patients with IGHV mutation. Interestingly, CLL-related lymphoid cell lines, but not stromal cells, failed to respond to the ligand-induced activation of the Wnt/β-catenin pathway. This opens the possibility that CLL cells use Wnt-3 to communicate with the cells in the microenvironment. We thus propose that the Wnt/β-catenin pathway plays a more complex role in CLL pathogenesis than previously anticipated., (© 2016 John Wiley & Sons Ltd.)
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- 2016
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13. TP53 mutation analysis in chronic lymphocytic leukemia: comparison of different detection methods.
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Kantorova B, Malcikova J, Smardova J, Pavlova S, Trbusek M, Tom N, Plevova K, Tichy B, Truong S, Diviskova E, Kotaskova J, Oltova A, Patten N, Brychtova Y, Doubek M, Mayer J, and Pospisilova S
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- Adult, Aged, Chromatography, High Pressure Liquid, Female, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Genes, p53, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation
- Abstract
TP53 gene defects represent a strong adverse prognostic factor for patient survival and treatment resistance in chronic lymphocytic leukemia (CLL). Although various methods for TP53 mutation analysis have been reported, none of them allow the identification of all occurring sequence variants, and the most suitable methodology is still being discussed. The aim of this study was to determine the limitations of commonly used methods for TP53 mutation examination in CLL and propose an optimal approach for their detection. We examined 182 CLL patients enriched for high-risk cases using denaturing high-performance liquid chromatography (DHPLC), functional analysis of separated alleles in yeast (FASAY), and the AmpliChip p53 Research Test in parallel. The presence of T53 gene mutations was also evaluated using ultra-deep next generation sequencing (NGS) in 69 patients. In total, 79 TP53 mutations in 57 (31 %) patients were found; among them, missense substitutions predominated (68 % of detected mutations). Comparing the efficacy of the methods used, DHPLC and FASAY both combined with direct Sanger sequencing achieved the best results, identifying 95 % and 93 % of TP53-mutated patients. Nevertheless, we showed that in CLL patients carrying low-proportion TP53 mutation, the more sensitive approach, e.g., ultra-deep NGS, might be more appropriate. TP53 gene analysis using DHPLC or FASAY is a suitable approach for mutation detection. Ultra-deep NGS has the potential to overcome shortcomings of methods currently used, allows the detection of minor proportion mutations, and represents thus a promising methodology for near future.
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- 2015
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