Tibor Vaszkó - Academia.edu (original) (raw)

Papers by Tibor Vaszkó

The human reference genome-based characteristics of the studied SFV positions and their ... more The human reference genome-based characteristics of the studied SFV positions and their variant ratios determined in 39 control samples grouped according to their variant ratio haplotype.</p

Relationship between a sample’s AZFc partial deletion/duplication status and its horizon... more Relationship between a sample’s AZFc partial deletion/duplication status and its horizontal variant ratio distribution.</p

The colored arrows show the direct and inverted repeats of AZFc. The colored arrowheads ... more The colored arrows show the direct and inverted repeats of AZFc. The colored arrowheads indicate the members of the eight gene families located in the region. The two rectangles enclose the gene family members eliminated by gr/gr deletion with two different breakpoints (g1/g2 versus r2/r4 deletion), respectively. The STS markers that have usually been analyzed in search for deletions are also shown.</p

Extended applicability of the class II/a DAZ3- and class II/b DAZ4-specific markers loca... more Extended applicability of the class II/a DAZ3- and class II/b DAZ4-specific markers located in Fragment II.</p

Extended applicability of DAZ1-specific A972 and DAZ4-specific C&... more Extended applicability of DAZ1-specific A972 and DAZ4-specific C1820.</p

Restricted applicability of class II/a markers.</p

The fifty-two samples sequenced form five distinct clusters according to the AUC ratio m... more The fifty-two samples sequenced form five distinct clusters according to the AUC ratio measured at SVF positions 1926 (A) and 1702 (C). Samples 1–5 are the duplication samples (referred to as Ydup_01–05 in the text), whereas samples 6–13 are the deletion samples (referred to as Ydel_06–13). Samples 14–52, each having one copy of all four DAZ family members, constitute the control panel. Representative electropherogram pictures of SVF positions 1926 (B) and 1702 (D) obtained in samples belonging to the distinct clusters are shown. The average (AUC ratioav) and standard deviation (StDev) of the AUC ratio values were calculated from all samples belonging to a cluster. Comparing with the AUC ratio–variant ratio relationship determined in control mixes, a variant ratio was assigned to each cluster at both positions. The AUC ratio (presented here as percentage) calculation is described in the Methods section.</p

Classification of DAZ family member-specific markers.</p

Restricted applicability of class II/b markers.</p

European Journal of Cancer, 2016

BRCA1/BRCA2 tests. Since next generation sequencing (NGS) opens new avenues to test many genes in... more BRCA1/BRCA2 tests. Since next generation sequencing (NGS) opens new avenues to test many genes in several patients, we aimed at identifying novel HBOC susceptibility alleles. Material and Method: Twenty-six patients were tested for the presence of germline mutations in 94 hereditary tumor-associated genes using the Illumina TruSight Cancer Panel kit. For the enrichment of the DNA libraries, the TruSight Rapid Capture kit was used, whereas sequencing was carried out on an Illumina MiSeq platform. An in-house-built workflow was created using online available tools for secondary and tertiary data analysis. The results were compared to the outcome of the manufacturer's MiSeq Reporter software analysis. In silico prediction tools were used to test for pathogenicity of selected variants. Results and Discussion: We have detected 3 clearly pathogenic variants in 3 genes in 4 patients. A nonsense mutation was found in the FANCM gene (c.1972C>T; p.Arg658*) in 2 patients, an insertion in FANCL (c.1096_1099dup; p.Thr367Asnfs*13) and a deletion in CHEK2 (c.277del; p.Trp93Glyfs*17) in one patient each. Using the XHMM software, we also detected a deletion in FANCM, whose validation is in progress. Additionally, 4 splice site variants, 10 missense variants and 2 in-frame micro-indels were predicted pathogenic by several in silico tools. Most of these candidate genes are related to DNA repair pathways and suspected to be involved in HBOC predisposition. Conclusion: Our study underlie the applicability of NGS in clinical diagnostic use, as we could identify rare susceptibilty alleles by this method. Three protein truncating variants and a copy number variant were found in three genes. These pathogenic alterations accounting for approximately 20% of the cases studied. We also detected several candidate variants, whose function as well as the magnitude of their risk modifying effect deserve further investigation. Acknowledgement: Our study was supported by the Hungarian Research Grant OTKA K-112228 to Edith Oláh. No conflict of interest. 157 Genetic and epigenetic evaluation of potentially important subtypes of clear cell sarcoma of kidney (CCSK)

European Journal of Cancer, 2016

deregulated biosynthesis of glycosphingolipids in cancer cells by epigenetic reprogramming. No co... more deregulated biosynthesis of glycosphingolipids in cancer cells by epigenetic reprogramming. No conflict of interest.

PLoS Genetics, 2013

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To i... more BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854,

The numbered arrows stand for the processes applied, the rectangles symbolize the result... more The numbered arrows stand for the processes applied, the rectangles symbolize the result of the respective process. The green rectangle shows the desired end-result of the analysis. Brown rectangles symbolize calibration data used to help derive variant ratios from AUC ratios. Red rectangles stand for input data required for stage 2 or, if there are marker associations, stage 3 analysis. Samples with different partial rearrangement types are indicated by three different shades of gray. The dashed arrow means that only deletion and duplication samples undergo stage 2 or stage 3 analysis. The large rectangle with transparent grey background contains the steps that are required for a complete analysis. The steps outside the large rectangle were used for the elaboration of the method. All processes are listed below. 1/ Aligning the sequences of the four DAZ genes extracted from the human reference genome in order to select amplifiable fragments which i) consist of four amplicons belonging to the four DAZ genes, respectively, and ii) contain as many SFV positions as possible (Fragments I and II) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.g002" target="_blank">Fig 2</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s001" target="_blank">S1 Fig</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s007" target="_blank">S5</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s009" target="_blank">S7</a> Files, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s011" target="_blank">S1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s012" target="_blank">S2</a> Tables). 2/ Amplification of selected regions in all individual samples to get Fragments I and II. 3/ Sequencing Fragments I and II in all individual samples. 4/ Preparing control plasmid mixtures by cloning Fragment I amplified from samples selected to contain every DAZ1, DAZ2, DAZ3 and DAZ4-specific variant in order to mimic wild-type, AZFc partial deletion and AZFc partial duplication samples having known variant ratios at each SFV position (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s014" target="_blank">S4 Table</a>). 5/ Amplification of selected regions to get Fragment I in control mixtures. 6/ Sequencing Fragment I in control mixtures. 7/ Measuring AUCs by ImageJ software and calculating the AUC ratio at each SFV position in every control mixture. 8/ Correlating the AUC ratios measured in control mixtures with known variant ratios (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s015" target="_blank">S5 Table</a>). 9/ Measuring AUCs and calculating the AUC ratio at each SFV position in all individual samples. 10/ Plotting AUC ratios throughout all samples for each studied position to visualize AUC ratio clustering (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.g003" target="_blank">Fig 3</a>). 11/ Assigning a variant ratio to each SFV position in all individual samples. 12/ Determining the horizontal variant ratio distribution in all individual samples. 13/ Grouping samples according to AZFc partial deletion/duplication status based on their horizontal variant ratio distribution (Tables <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.t001" target="_blank">1</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.t004" target="_blank">4</a>). The results of this step were validated by a generally accepted DAZ dosage test (not shown) and two multiplex PCRs amplifying six sY markers (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s002" target="_blank">S2 Fig</a>). 14/ Specifying the variant ratios that remained ambiguous on the basis of the AUC ratio (electropherogram picture) in step 11 (0:2x, x:x and 2x:0 positions). 15/ Deducing the copy number of the specific variant at each SFV position in all individual samples from the relevant variant ratio. 16/ Cloning Fragments I and II in four selected control samples to separate the four amplicons derived from the four DAZ family members, respectively. 17/ Sequencing an appropriate number of colonies in order to study the co-segregation of DAZ family member-specific variants, i.e. the fulfillment of requirement (c) imposed on an ideal marker (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s016" target="_blank">S6 Table</a>).18/ Determining the vertical variant ratio distribution throughout all control samples at each studied SFV position. 19/ Determining p1 and p2 values on the basis of the vertical variant ratio distribution at each…

Panel A: DAZ1 and DAZ2. Panel B: DAZ3 and DAZ4. The figure was captured from the UCSC Ge... more Panel A: DAZ1 and DAZ2. Panel B: DAZ3 and DAZ4. The figure was captured from the UCSC Genome Browser after uploading an appropriate BED file (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163936#pone.0163936.s009" target="_blank">S7 File</a>). Below the scale, chromosome Y coordinates according to the human genome build NCBI36/hg18 are shown. Below the RefSeq Genes label, the structure of the DAZ family members are illustrated with the exons indicated by perpendicular lines. The aligned arrowheads in the thick green line show the direction of the coding sequence. Variants presented in red and blue colors are specific and non-specific for the corresponding DAZ family members, respectively. For non-specific variants, a digit in square brackets indicates the DAZ family member for which the relevant SFV position contains a specific variant. The numbers in the variants' name indicate the variants' location in Fragments I or II.</p

PLoS Genetics, 2013

International Journal of Molecular Sciences

Large genomic rearrangements (LGRs) affecting one or more exons of BRCA1 and BRCA2 constitute a s... more Large genomic rearrangements (LGRs) affecting one or more exons of BRCA1 and BRCA2 constitute a significant part of the mutation spectrum of these genes. Since 2004, the National Institute of Oncology, Hungary, has been involved in screening for LGRs of breast or ovarian cancer families enrolled for genetic testing. LGRs were detected by multiplex ligation probe amplification method, or next-generation sequencing. Where it was possible, transcript-level characterization of LGRs was performed. Phenotype data were collected and analyzed too. Altogether 28 different types of LGRs in 51 probands were detected. Sixteen LGRs were novel. Forty-nine cases were deletions or duplications in BRCA1 and two affected BRCA2. Rearrangements accounted for 10% of the BRCA1 mutations. Three exon copy gains, two complex rearrangements, and 23 exon losses were characterized by exact breakpoint determinations. The inferred mechanisms for LGR formation were mainly end-joining repairs utilizing short direc...

Anticancer research, 2009

The aim of this study was to elucidate the anticancer activity of Ribavirin, an antiviral drug an... more The aim of this study was to elucidate the anticancer activity of Ribavirin, an antiviral drug and a known inhibitor of inositide-5'-monophosphate dehydrogenase. Using human cancer cell lines, the potential of the drug to inhibit growth and induce the apoptotic and differentiation pathways was investigated by cytological methods. The effect exerted upon gene expression was studied in K562 cells by Q-PCR. Treatment with Ribavirin resulted in a significant growth inhibition (IC(50)=15 microM) via activating apoptosis and the differentiation pathway in K562 cells. It also modulated the expression of about 60 out of 85 genes having roles in cell proliferation, purine biosynthesis, translation initiation, oncogenic signaling and cell survival (p<0.05). Ribavirin is a potent anticancer agent, being a strong inducer of apoptosis and a moderate inducer of differentiation in K562 cells. These effects are mediated through the modulation of key molecular and metabolic pathways.

Extended applicability of DAZ1-specific A972 and DAZ4-specific C&... more Extended applicability of DAZ1-specific A972 and DAZ4-specific C1820.</p

Restricted applicability of class II/a markers.</p

Classification of DAZ family member-specific markers.</p

Restricted applicability of class II/b markers.</p

European Journal of Cancer, 2016

PLoS Genetics, 2013

International Journal of Molecular Sciences

Anticancer research, 2009