A5039402772- Multiple Myeloma Research and Treatments
- Genomic variations and chromosomal abnormalities
- Chromosomal and Genetic Variations
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Ubiquitin and proteasome pathways
- Immunodeficiency and Autoimmune Disorders
- CRISPR and Genetic Engineering
- PI3K/AKT/mTOR signaling in cancer
- Cancer Treatment and Pharmacology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Monoclonal and Polyclonal Antibodies Research
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Chronic Lymphocytic Leukemia Research
- Genetic factors in colorectal cancer
- Chronic Myeloid Leukemia Treatments
- Viral-associated cancers and disorders
- Epigenetics and DNA Methylation
- Genomics and Rare Diseases
Newcastle University
2019-2024
University of Arkansas for Medical Sciences
2017-2019
Masaryk University
2009-2017
University Hospital Brno
2014-2017
University of Ostrava
2016
At the molecular level, myeloma is characterized by copy number abnormalities and recurrent translocations into immunoglobulin heavy chain locus. Novel methods, such as massively parallel sequencing, have begun to describe pattern of tumor-acquired mutations, but their clinical relevance has yet be established.We performed whole-exome sequencing for 463 patients who presented with were enrolled onto National Cancer Research Institute Myeloma XI trial, whom complete cytogenetic outcome data...
Abstract De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de an important severe male infertility and explain portion of the genetic causes this understudied disorder. To test hypothesis, we utilize trio-based exome sequencing cohort 185 infertile males their unaffected parents. Following systematic analysis, 29 145 rare (MAF < 0.1%) protein-altering classified as possibly causative phenotype. observed significant...
Abstract Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering (SMM). We interrogate the whole genome sequence (WGS) profile 18 MGUS and compare them with those from 14 SMMs 80 MMs. show that cases a non-progressing, stable condition ( n = 15) are characterized later initiation in patient’s life absence defining genomic events including: chromothripsis, templated insertions,...
STAT2 R148W impairs an essential regulatory function of STAT2, revealing the damage wreaked by excessive IFNα/β activity.
Monoclonal gammopathy of undetermined significance is a pre-malignant precursor multiple myeloma with 1% risk progression per year. Although targeted analyses have shown the presence specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little known about molecular mechanism malignant transformation. We performed whole exome sequencing together comparative genomic hybridization plus single nucleotide polymorphism array analysis...
Abstract Background Neurodevelopmental disorders (NDDs) and/or associated multiple congenital abnormalities (MCAs) represent a genetically heterogeneous group of conditions with an adverse prognosis for the quality intellectual and social abilities common daily functioning. The rapid development exome sequencing (ES) techniques, together trio-based analysis, nowadays leads to up 50% diagnostic yield. Therefore, it is considered as state-of-the-art approach in these diagnoses. Results In our...
is a widely acting transcription factor and its deregulation crucial event in many human cancers.
Abstract Monoclonal gammopathy of undetermined significance ( MGUS ) is a benign condition with an approximate 1% annual risk symptomatic plasma cell disorder development, mostly to multiple myeloma MM ). We performed genomewide screening copy‐number alterations CNA s) in 90 and 33 patients using high‐density DNA microarrays. identified s smaller proportion (65.6%) than (100.0%, P = 1.31 × 10 −5 showed median number lower (3, range 0–22) (13, 4–38, 1.82 −10 In the cohort, most frequent...
Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin- MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules unproven efficacy. Here we compare the molecular characteristics these conditions investigate historic clinical outcome data. We identified 90 cases registered a national BCP-ALL trial/registry. When present, material underwent...
Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation progression. In this work, using CoMMpass dataset, we show that structural variants (SV) occur in a nonrandom fashion throughout genome with an increased frequency t(4;14), RB1, or TP53 mutated cases reduced t(11;14) cases. By mapping sites of chromosomal rearrangements topologically associated domains significantly upregulated genes by RNAseq identify...
Characteristic recurrent copy number aberrations (CNAs) play a key role in multiple myeloma (MM) pathogenesis and have important prognostic significance for MM patients. Array-based comparative genomic hybridization (aCGH) provides powerful tool genome-wide classification of CNAs thus should be implemented into routine diagnostics. We demonstrate the possibility effective utilization oligonucleotide-based aCGH 91 Chromosomal associated with effect on prognosis were initially evaluated by...
Broad domains of H3K4 methylation have been associated with consistent expression tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain–associated genes in healthy human thymic T populations a collection acute lymphoblastic leukemia (T-ALL) primary samples lines. We found that are highly dynamic throughout differentiation, their varying breadth allows the distinction between normal neoplastic cells. Although preferentially associate identity thymocytes,...
Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes activated by juxtaposition with enhancers, often called enhancer hijacking . We analyzed the epigenomic consequences rearrangements between super-enhancers immunoglobulin heavy locus ( IGH ) and proto-oncogene CCND1 that common in B cell malignancies. By integrating BLUEPRINT data DNA breakpoint detection, we characterized normal chromatin landscape human its dynamics after pathological...
Genomic rearrangements are known to result in proto-oncogene deregulation many cancers, but the link 3D genome structure remains poorly understood. Here, we used highly predictive heteromorphic polymer (HiP-HoP) model predict chromatin conformations at CCND1 healthy and malignant B cells. After confirming that gives good predictions of Hi-C data for nonmalignant human cell–derived cell line GM12878, generated two cancer lines, U266 Z-138. These possess involving immunoglobulin heavy locus (...
A 3-year-old girl of nonconsanguineous healthy parents presented with cervical and mediastinal lymphadenopathy due to Mycobacterium fortuitum infection. Routine blood analysis showed normal hemoglobin, neutrophils, platelets but profound mononuclear cell deficiency (monocytes < 0.1 × 109/L; B cells 78/μL; NK 48/μL). 548 902-bp region containing GATA2 was sequenced by targeted capture deep sequencing. This revealed a de novo 187-kb duplication the entire locus, maternally inherited copy...
Pathogenic variants affecting the <em>BLM</em> gene are responsible for manifestation of extremely rare cancer‑predisposing Bloom syndrome. The present study reports on a case an infant with congenital hypotrophy, short stature and abnormal facial appearance. Initially she was examined using routine molecular diagnostic algorithm, including cytogenetic analysis her karyotype, microarray methylation‑specific MLPA, however, remained undiagnosed level. Therefore, parents were enrolled in...
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition with risk malignant conversion.With the aim to estimate cumulative MGUS progression hematologic malignancies, we analyzed nationwide population-based cohort 1887 patients from Czech Registry Gammopathies (RMG) between 2007 and 2013.During follow-up period (median 4 years; range 0.6-34.8), malignancies was observed in 8.6% (162 1887) patients. Factors associated were as follows: M-protein concentration ≥1.5...
Alport syndrome with intellectual disability (ATS-ID, AMME complex; OMIM #300194) is an X-linked contiguous gene deletion associated Xq22.3 locus mainly characterized by hematuria, renal failure, hearing loss/deafness, neurodevelopmental disorder (NDD), midface retrusion, and elliptocytosis. It thought that ATS-ID caused the loss of function COL4A5 (ATS) FACL4 (ACSL4) genes through interstitial (micro)deletion chromosomal band Xq22.3. We report detailed phenotypic description results from...
Abstract The myeloma overexpressed gene ( MYEOV ) has been proposed to be a proto-oncogene due high RNA transcript levels found in multiple cancers, including myeloma, breast, lung, pancreas and esophageal cancer. presence of an open reading frame (ORF) humans other primates suggests protein-coding potential. Yet, we still lack evidence functional protein. It remains undetermined how overexpression affects cancerous tissues. In this work, show that originated may function as enhancer,...