7 results on '"Martina Zatopkova"'
Search Results
2. Mutation landscape of multiple myeloma measurable residual disease: identification of targets for precision medicine
- Author
-
Lucie Broskevicova, Kateřina Growková, Jana Filipova, Jiří Minařík, Roman Hájek, Ludek Pour, Giovanni Stracquadanio, Lucie Rihova, Fedor Kryukov, Juli R. Bagó, Lubica Harvanova, Zuzana Chyra, Lucie Cerna, Michal Simicek, Vladimir Maisnar, Martina Zatopkova, Renata Bezdekova, Matous Hrdinka, David Žihala, Alexandra Jungova, Viola Fanfani, Tereza Sevcikova, Jana Smejkalová, Tereza Popkova, Anjana Anilkumar Sithara, and Tomas Jelinek
- Subjects
Neoplasm, Residual ,business.industry ,precision medicine ,MEDLINE ,Hematology ,Computational biology ,Disease ,medicine.disease ,Precision medicine ,Residual ,multiple myeloma ,hemic and lymphatic diseases ,Mutation ,Mutation (genetic algorithm) ,Commentary ,medicine ,Humans ,Identification (biology) ,Precision Medicine ,mutation ,Multiple Myeloma ,business ,residual tumor ,Multiple myeloma - Abstract
Multiple myeloma (MM) measurable residual disease (MRD) persisting after treatment is an adverse prognostic factor for progression free survival (PFS) and overall survival.1Genomic mutations occurred in the remaining clonal aberrant plasma cells (A-PCs) are linked to the development of drug resistance and disease relapse.2 Thus, personalised treatment based on the genomic profile of MRD could be highly beneficial and ultimately increase patients’ survival. However, while large-scale sequencing studies have characterised the genome of many malignancies including MM,3–8 the genomic mutations present in MM MRD are at the beginning of investigation.9 Here, we set up an exome sequencing analysis to identify genomic mutations characteristic for MM MRD and explore if they could mediate drug response, resistance or disease progression.
- Published
- 2022
3. Heterogenous mutation spectrum and deregulated cellular pathways in aberrant plasma cells underline molecular pathology of light-chain amyloidosis
- Author
-
Jana Filipova, Martin Mistrik, Ludek Pour, Martin Mokrejs, Gabor Mikala, Lucie Brozova, Artur Jurczyszyn, Roman Hájek, Lukas Stejskal, Michal Simicek, Martin Stork, Katerina Growkova, Zuzana Chyra, Martina Zatopkova, Petr Vojta, Pawel Robak, Jakub Dębski, Marian Hajduch, Anna Czyż, Agnieszka Barchnicka, Matous Hrdinka, Eva Budinská, Tereza Sevcikova, Janka Puterova, Aneta Mikulasova, Lidia Usnarska-Zubkiewicz, Tomas Jelinek, Wiesław Wiktor Jędrzejczak, Fedor Kryukov, Lubica Harvanova, Sebastian Grosicki, Alexandra Jungova, Anna Waszczuk-Gajda, and Gareth J. Morgan
- Subjects
Amyloid ,Plasma Cells ,Immunoglobulin light chain ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,medicine ,AL amyloidosis ,Humans ,Immunoglobulin Light-chain Amyloidosis ,Pathology, Molecular ,Letters to the Editor ,Multiple myeloma ,030304 developmental biology ,0303 health sciences ,Mutation ,biology ,Chemistry ,Molecular pathology ,Amyloidosis ,AL AMYLOIDOSIS ,Hematology ,medicine.disease ,3. Good health ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Immunoglobulin Light Chains ,Antibody - Abstract
Light-chain (AL) amyloidosis (ALA) is a rare but fatal monoclonal gammopathy (MG) causing organ and tissue damage resulting from the deposition of misfolded immunoglobulin free light chains in the form of amyloid fibrils.1 In some cases, ALA coexists with multiple myeloma (MM) (ALA+MM), which is the second most common blood cancer and is caused by the proliferation of clonal plasma cells (PC).2 Due to insufficient knowledge of ALA and ALA+MM biology, therapeutic options have mirrored treatment regimens of MM, which focus on the elimination of clonal PC.3,4 We investigated the mutation and gene expression profiles in clonal aberrant PC (aPC) in order to better understand ALA and ALA+MM etiology and to clarify the molecular differences between individual MG diagnoses.
- Published
- 2021
4. Dissecting the heritable risk of breast cancer: From statistical methods to susceptibility genes
- Author
-
Viola Fanfani, Martina Zatopkova, Giovanni Stracquadanio, Francesco Pezzella, and Adrian L. Harris
- Subjects
0301 basic medicine ,Cancer Research ,Population ,Single-nucleotide polymorphism ,Genome-wide association study ,Breast Neoplasms ,medicine.disease_cause ,Bioinformatics ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,medicine ,Biomarkers, Tumor ,SNP ,Humans ,Genetic Predisposition to Disease ,education ,Genetic association ,education.field_of_study ,Models, Statistical ,business.industry ,Cancer ,medicine.disease ,Prognosis ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Carcinogenesis ,business ,Genome-Wide Association Study - Abstract
Decades of research have shown that rare highly penetrant mutations can promote tumorigenesis, but it is still unclear whether variants observed at high-frequency in the broader population could modulate the risk of developing cancer. Genome- wide Association Studies (GWAS) have generated a wealth of data linking single nucleotide polymorphisms (SNPs) to increased cancer risk, but the effect of these mutations are usually subtle, leaving most of cancer heritability unexplained. Understanding the role of high-frequency mutations in cancer can provide new intervention points for early diagnostics, patient stratification and treatment in malignancies with high prevalence, such as breast cancer.Here we review state-of-the-art methods to study cancer heritability using GWAS data and provide an updated map of breast cancer susceptibility loci at the SNP and gene level.
- Published
- 2019
5. Current applications of multiparameter flow cytometry in plasma cell disorders
- Author
-
Tereza Sevcikova, Renata Bezdekova, Roman Hájek, Tomas Jelinek, Martina Zatopkova, Michal Simicek, Bruno Paiva, and Leire Burgos
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Paraproteinemias ,Review ,Plasma cell ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Citometría ,Internal medicine ,medicine ,Humans ,Multiple myeloma ,medicine.diagnostic_test ,business.industry ,Waldenstrom macroglobulinemia ,Hematology ,Flow Cytometry ,medicine.disease ,Minimal residual disease ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Monoclonal ,Erratum ,Ciencias de la Salud::Hematología [Materias Investigacion] ,business ,Cytometry ,030215 immunology - Abstract
Multiparameter flow cytometry (MFC) has become standard in the management of patients with plasma cell (PC) dyscrasias, and could be considered mandatory in specific areas of routine clinical practice. It plays a significant role during the differential diagnostic work-up because of its fast and conclusive readout of PC clonality, and simultaneously provides prognostic information in most monoclonal gammopathies. Recent advances in the treatment and outcomes of multiple myeloma led to the implementation of new response criteria, including minimal residual disease (MRD) status as one of the most relevant clinical endpoints with the potential to act as surrogate for survival. Recent technical progress led to the development of next-generation flow (NGF) cytometry that represents a validated, highly sensitive, cost-effective and widely available technique for standardized MRD evaluation, which also could be used for the detection of circulating tumor cells. Here we review current applications of MFC and NGF in most PC disorders including the less frequent solitary plasmocytoma, light-chain amyloidosis or Waldenström macroglobulinemia.
- Published
- 2017
- Full Text
- View/download PDF
6. Whole Exome Sequencing of Residual Disease in Multiple Myeloma: Searching for Novel Therapeutic Targets
- Author
-
Roman Hájek, Lucie Říhová, Katerina Growkova, Martin Mistrik, Vladimir Maisnar, Jiri Minarik, Renata Bezděková, Tomas Jelinek, Jana Smejkalová, Alexandra Jungova, Jana Filipova, Fedor Kryukov, Martina Zatopkova, Zuzana Kufova, Tereza Sevcikova, Giovanni Stracquadanio, Michal Simicek, and Ludek Pour
- Subjects
Oncology ,Immunoglobulin gene ,Neuroblastoma RAS viral oncogene homolog ,medicine.medical_specialty ,Immunology ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Minimal residual disease ,Germline mutation ,Internal medicine ,medicine ,1000 Genomes Project ,Exome ,Exome sequencing ,Reference genome - Abstract
Introduction: Multiple myeloma (MM) is a plasma cell dyscrasia causing damage of multiple organs with fatal consequences for patients. Despite the success of modern therapies eliminating a vast bulk of the aberrant cells, surviving residual clones eventually lead to the relapse of the disease. Accumulation of genomic alterations during the stage of minimal residual disease (MRD) likely contributes to a selective grow advantage and survival under the drug pressure. Identification of specific mutations in MM patients with MRD can provide unique opportunities to target the residual plasma cell clones. Here we present the first whole exome sequencing (WES) analysis of 22 MM samples of patients with MRD that identified 814 mutated genes with 4% of genes previously implicated in the pathogenesis of MM. Methods: Aberrant plasma cells (A-PCs) and peripheral blood (PB) were collected from patients after signing informed consent form. Presence of MRD was assessed with EuroFlow protocol and A-PCs were sorted out from bone marrow according to their pathological immunophenotype based on the expression of antigens CD38, CD45, CD19 and CD56. DNA from A-PCs was isolated and amplified by Repli-g Single cell kit (QIAGEN). Sequencing libraries were prepared using SureSelect Human All Exon V6 Kit (Agilent Technologies) and sequenced by Macrogen Inc. on Illumina HiSeq 4000 platform with average coverage 50x and 2x 100bp read length. Sequencing data were processed using the Bcbio framework following the standard workflow for tumor-matched-normal studies. Specifically, reads were mapped to the human reference genome GRCh37, successively marking duplicates using Picard. Germline mutations were identified using GATK HaplotypeCaller, whereas somatic mutations were identified using MuTect2 reporting as significant variants observed in at least 5 reads and minimum allele frequency of 10%. Variants in homopolymer regions longer than 5 nucleotides were filtered out. The final set of calls were further characterised by assessing their functional impact using snpEff and by annotating each variant using data from 1000 Genomes Phase 3, ExAC, and ClinVar. We then used OncodriveCLUST to identify putative oncogenic genes, and later compared these results with a literature curated list of MM driver genes (Weaver & Tariman, 2017). Results: Our dataset comprises 22 samples from 21 patients (one patient was sampled in two time points) with MM MRD, who received bortezomib-based regimen (age 41-71, average 59 years, 11/22 males, 10/22 females). 8 patients reached complete response, 9 patients had very good partial response and 4 patients had partial response. In our analysis, we detected 1,014 tumour somatic variants (8-287 per sample, median 36), most of them being missense mutations (676/1014), splice site mutations (145/1014) and frameshift insertions (134/1014). The variants affected a total of 814 genes, 97 genes were shared in at least two samples. The most frequently mutated genes were KIAA1211 (11/22), the immunoglobulin gene IGLV3-1 (8/22), apoptotic chromatin condensation inducer ACIN1 (7/22) and CCR4-associated factor 3 CNOT3 (7/22). We also identified 32 genes known to be mutated in MM in 64% of our samples (14/22). We found mutations shared by at least 2 samples in KRAS (4/22), DIS3 (3/22), TRAF3 (3/22), NRAS (2/22), ANK2 (2/22), BRAF (2/22) and RBM15 (2/22). Further analysis with OncodriveCLUST identified 18 putative oncogenic genes (FDR < 0.1), including KRAS, DIS3, ACIN1. Conclusion: We presented the first whole exome study of MM MRD, providing a characterisation of the mutations observed in A-PCs. We overcame problem with low amount of A-PCs in this disease stage by using whole genome amplification and a highly customised bioinformatic analysis pipeline. Our study suggests that A-PCs are characterised by new MM MRD specific set of mutated genes, along with the presence of mutations in well-known multiple myeloma cancer driver genes. This offers a great potential for design of novel precise treatments targeting MRD after standard MM therapies. Supported by Ministry of Health of the Czech Republic (17-30089A, CZ-DRO-FNOs/2016) and Ministry of Education of the Czech Republic (SGS18/PřF/2017-2018) Disclosures Kryukov: JSC BIOCAD: Employment. Maisnar:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Hajek:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Research Funding.
- Published
- 2018
7. Whole Exome Sequencing of Aberrant Plasma Cells in a Patient with Multiple Myeloma Minimal Residual Disease
- Author
-
Fedor Kryukov, Tereza Sevcikova, Marian Hajduch, Martina Zatopkova, Zuzana Kufova, Luděk Pour, Lucie Říhová, Renata Bezděková, Jana Filipova, Alexandra Jungova, Petr Vojta, Kateřina Growková, Jana Smejkalová, Roman Hájek, Vladimir Maisnar, Tomas Jelinek, Jiří Minařík, and Michal Simicek
- Subjects
Neoplasm, Residual ,Plasma Cells ,Plasma cell dyscrasia ,Biology ,Bioinformatics ,DNA sequencing ,GTP Phosphohydrolases ,Bortezomib ,symbols.namesake ,Antigens, CD ,Exome Sequencing ,medicine ,Humans ,Exome ,Multiple myeloma ,Exome sequencing ,Sanger sequencing ,Membrane Proteins ,medicine.disease ,Minimal residual disease ,Oncology ,Drug Resistance, Neoplasm ,symbols ,Cancer research ,Multiple Myeloma ,medicine.drug - Abstract
Multiple myeloma is a plasma cell dyscrasia. It is the second most common hematological malignancy which is characterized by proliferation of clonal plasma cells producing harmful monoclonal immunoglobulin. Despite treatment modalities greatly evolved during the last decade, small amount of aberrant residual cells reside in patients after therapy and can cause relapse of the disease. Characterization of the residual, resistant clones can help to reveal important therapeutic targets for application of effective and precious treatment. We use CD38, CD45, CD56 and CD19 sorted aberrant plasma cells to perform next generation sequencing of their exome. Among the 213 genes in which at least one variant was present, the most interesting was found gene NRAS, one of the most often mutated gene in multiple myeloma, and homologs of 88 gene panel previously used for multiple myeloma sequencing among which was a gene previously identified as gene meaningful in bortezomib resistance. Nevertheless, the results of next generation exome sequencing need to be interpreted with caution, since they rely on bioinformatical analysis, which is still being optimized. The results of next generation sequencing will also have to be confirmed by Sanger sequencing. Final results supported by larger cohort of patients will be published soon.Key words: multiple myeloma - minimal residual disease - exome - next generation sequencing.
- Published
- 2017
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.