TY - JOUR AU - Bátai, Bence AU - Kiss, Laura AU - Varga, Luca Petra AU - Nagy, Ákos AU - Househam, Jacob AU - Baker, Ann-Marie AU - László, Tamás AU - Udvari, Anna AU - Horváth, Róbert AU - Nagy, Tibor AU - Csomor, Judit AU - Szakonyi, József AU - Schneider, Tamás AU - Graham, Trevor A AU - Alpár, Donát AU - Fitzgibbon, Jude AU - Szepesi, Ágota AU - Bödör, Csaba TI - Profiling of copy number alterations using low-coverage whole-genome sequencing informs differential diagnosis and prognosis in primary cutaneous follicle center lymphoma. JF - MODERN PATHOLOGY J2 - MODERN PATHOL VL - 37 PY - 2024 IS - 5 PG - 13 SN - 0893-3952 DO - 10.1016/j.modpat.2024.100465 UR - https://m2.mtmt.hu/api/publication/34729974 ID - 34729974 N1 - Export Date: 24 April 2024 CODEN: MODPE AB - Primary cutaneous follicle center lymphoma (PCFCL) has an excellent prognosis using local treatment, while nodal follicular lymphoma (nFL) occasionally presenting with cutaneous spread, often requires systemic therapy. Distinction of the two diseases based on histopathology alone might be challenging. Copy number alterations (CNAs) have scarcely been explored on a genome-wide scale in PCFCL, yet they might serve as potential biomarkers during differential diagnosis and risk stratification. Low-coverage whole genome sequencing (lcWGS) is a robust, high-throughput method for genome-wide copy number profiling. In this study, we analyzed 28 PCFCL samples from 20 patients and compared the copy number profiles to a cohort of diagnostic samples of 64 nFL patients. Although the copy number profile of PCFCL was similar to that of nFL, PCFCL lacked amplifications of 18q, with the frequency peaking at 18q21.33 in nFL cases involving the BCL2 locus (PCFCL: 5.0% vs. nFL: 31.3%, p=0.018, Fisher's exact test). Development of distant cutaneous spread was significantly associated with higher genomic instability including the proportion of genome altered (0.02 vs. 0.13, p=0.033) and number of CNAs (2 vs. 9 p=0.017), as well as the enrichment of 2p22.2-p15 amplification involving REL and XPO1 (6.3% vs. 60.0%, p=0.005), 3q23-q24 amplification (0.0% vs. 50.0%, p=0.004), 6q16.1-q23.3 deletion (6.3% vs. 50.0%, p=0.018) and 9p21.3 deletion covering CDKN2A and CDKN2B loci (0.0% vs. 40.0%, p=0.014, all Fisher's exact test) in PCFCL. Analysis of sequential tumor samples in two cases harboring an unfavorable clinical course pointed to the acquisition of 2p amplification in the earliest common progenitor underlining its pivotal role in malignant transformation. By performing genome-wide copy number profiling on the largest patient cohort to date, we identified distinctive CNA alterations conceivably facilitating the differential diagnosis of PCFCL and secondary cutaneous involvement of nFL, and potentially aiding the risk stratification of patients with PCFCL in the future. LA - English DB - MTMT ER - TY - JOUR AU - Noerenberg, Daniel AU - Briest, Franziska AU - Hennch, Cornelius AU - Yoshida, Kenichi AU - Hablesreiter, Raphael AU - Takeuchi, Yasuhide AU - Ueno, Hiroo AU - Staiger, Annette M AU - Ziepert, Marita AU - Asmar, Fazila AU - Locher, Benjamin N AU - Tóth, Erika AU - Weber, Thomas AU - Amini, Rose-Marie AU - Klapper, Wolfram AU - Bouzani, Maria AU - Poeschel, Viola AU - Rosenwald, Andreas AU - Held, Gerhard AU - Campo, Elías AU - Ishaque, Naveed AU - Stamatopoulos, Kostas AU - Kanellis, George AU - Anagnostopoulos, Ioannis AU - Bullinger, Lars AU - Goldschmidt, Neta AU - Zinzani, Pier Luigi AU - Bödör, Csaba AU - Rosenquist, Richard AU - Vassilakopoulos, Theodoros P AU - Ott, German AU - Ogawa, Seishi AU - Damm, Frederik TI - Genetic Characterization of Primary Mediastinal B-Cell Lymphoma. Pathogenesis and Patient Outcomes TS - Pathogenesis and Patient Outcomes JF - JOURNAL OF CLINICAL ONCOLOGY J2 - J CLIN ONCOL VL - 42 PY - 2024 IS - 4 SP - 452 EP - 466 PG - 15 SN - 0732-183X DO - 10.1200/JCO.23.01053 UR - https://m2.mtmt.hu/api/publication/34430138 ID - 34430138 N1 - Department of Hematology, Oncology and Cancer Immunology, Campus Virchow, Charité—Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan Division of Cancer Evolution, National Cancer Center Research Institute, Tokyo, Japan Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology Stuttgart, University of Tuebingen, Stuttgart, Germany Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Department of Surgical and Molecular Pathology, National Tumour Biology Laboratory, National Institute of Oncology, Budapest, Hungary Department of Internal Medicine IV, Haematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Halle, Germany Department of Immunology, Genetics and Pathology, Uppsala University, University Hospital, Uppsala, Sweden Department of Pathology, Hematopathology Section and Lymph Node Registry, Universitätsklinikum Schleswig-Holstein, Kiel, Germany Department of Hematology and Lymphoma, BMTU, Evaggelismos General Hospital, Athens, Greece Department of Internal Medicine 1 (Oncology, Hematology, Clinical Immunology, and Rheumatology), Saarland University Medical School, Homburg, Germany Institute of Pathology, University of Würzburg and Comprehensive Cancer Center (CCC) Mainfranken, Würzburg, Germany Department Internal Medicine I, Westpfalzklinikum Kaiserslautern, Kaiserslautern, Germany Centro de Investigacion Biomedica en Red en Oncologia (CIBERONC), Madrid, Spain Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Center of Digital Health, Berlin, Germany Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece Department of Hematopathology, Evangelismos General Hospital, Athens, Greece Department of Pathology, Charité—Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Hadassah-Hebrew University Medical Center, Jerusalem, Israel IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli, Bologna, Italy Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy HCEMM-SE Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden Department of Hematology and Bone Marrow Transplantation, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece Department of Medicine, Centre for Haematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan Export Date: 20 February 2024; Cited By: 0; Correspondence Address: F. Damm; Department of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Berlin, Augustenburger Platz 1, 13353, Germany; email: frederik.damm@charite.de; CODEN: JCOND AB - Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive lymphoma predominantly affecting young female patients. Large-scale genomic investigations and genetic markers for risk stratification are lacking.To elucidate the full spectrum of genomic alterations, samples from 340 patients with previously untreated PMBCL were investigated by whole-genome (n = 20), whole-exome (n = 78), and targeted (n = 308) sequencing. Statistically significant prognostic variables were identified using a multivariable Cox regression model and confirmed by L1/L2 regularized regressions.Whole-genome sequencing revealed a commonly disrupted p53 pathway with nonredundant somatic structural variations (SVs) in TP53-related genes (TP63, TP73, and WWOX) and identified novel SVs facilitating immune evasion (DOCK8 and CD83). Integration of mutation and copy-number data expanded the repertoire of known PMBCL alterations (eg, ARID1A, P2RY8, and PLXNC1) with a previously unrecognized role for epigenetic/chromatin modifiers. Multivariable analysis identified six genetic lesions with significant prognostic impact. CD58 mutations (31%) showed the strongest association with worse PFS (hazard ratio [HR], 2.52 [95% CI, 1.50 to 4.21]; P < .001) and overall survival (HR, 2.33 [95% CI, 1.14 to 4.76]; P = .02). IPI high-risk patients with mutated CD58 demonstrated a particularly poor prognosis, with 5-year PFS and OS rates of 41% and 58%, respectively. The adverse prognostic significance of the CD58 mutation status was predominantly observed in patients treated with nonintensified regimens, indicating that dose intensification may, to some extent, mitigate the impact of this high-risk marker. By contrast, DUSP2-mutated patients (24%) displayed durable responses (PFS: HR, 0.2 [95% CI, 0.07 to 0.55]; P = .002) and prolonged OS (HR, 0.11 [95% CI, 0.01 to 0.78]; P = .028). Upon CHOP-like treatment, these patients had very favorable outcome, with 5-year PFS and OS rates of 93% and 98%, respectively.This large-scale genomic characterization of PMBCL identified novel treatment targets and genetic lesions for refined risk stratification. DUSP2 and CD58 mutation analyses may guide treatment decisions between rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. LA - English DB - MTMT ER - TY - JOUR AU - László, Tamás AU - Kotmayer, Lili AU - Fésüs, Viktória AU - Hegyi, Lajos AU - Gróf, Stefánia AU - Nagy, Ákos AU - Kajtár, Béla AU - Balogh, Alexandra AU - Weisinger, Júlia AU - Masszi, Tamás AU - Nagy, Zsolt AU - Farkas, Péter AU - Demeter, Judit AU - Istenes, Ildikó AU - Szász, Róbert AU - Gergely, Lajos AU - Sulák, Adrienn AU - Borbényi, Zita AU - Lévai, Dóra AU - Schneider, Tamás AU - Pettendi, Piroska AU - Bodai, Emese AU - Szerafin, László AU - Rejtő, László AU - Bátai, Árpád AU - Dömötör, Mária Á AU - Sánta, Hermina AU - Plander, Márk AU - Szendrei, Tamás AU - Hamed, Aryan AU - Lázár, Zsolt AU - Pauker, Zsolt AU - Radványi, Gáspár AU - Kiss, Adrienn AU - Körösmezey, Gábor AU - Jakucs, János AU - Dombi, Péter J AU - Simon, Zsófia AU - Klucsik, Zsolt AU - Gurzó, Mihály AU - Tiboly, Márta AU - Vidra, Tímea AU - Ilonczai, Péter AU - Bors, András AU - Andrikovics, Hajnalka AU - Egyed, Miklós AU - Székely, Tamás AU - Masszi, András AU - Alpár, Donát AU - Matolcsy, András AU - Bödör, Csaba TI - Low‐burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation JF - JOURNAL OF PATHOLOGY: CLINICAL RESEARCH J2 - J PATHOL CLIN RES VL - 10 PY - 2024 IS - 1 PG - 12 SN - 2056-4538 DO - 10.1002/cjp2.351 UR - https://m2.mtmt.hu/api/publication/34399695 ID - 34399695 N1 - Funding Agency and Grant Number: EU [739593]; Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund [K21_137948, FK20_134253, TKP2021-EGA-24, TKP2021-NVA-15, EFOP-3.6.3-VEKOP-16-2017-00009, NKP-22-3-II-SE-21]; Hungarian Academy of Sciences [BO/00125/22]; Elixir Hungary Funding text: This work was funded by the EU's Horizon 2020 Research and Innovation Program under grant agreement No. 739593, by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the K21_137948, FK20_134253, TKP2021-EGA-24, and TKP2021-NVA-15 funding schemes, the EFOP-3.6.3-VEKOP-16-2017-00009 and & Uacute;NKP-22-3-II-SE-21 grants, the Janos Bolyai Research Scholarship program (BO/00125/22) of the Hungarian Academy of Sciences, and Elixir Hungary. AB - TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next‐generation sequencing (NGS)‐based studies have identified frequent low‐burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low‐burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS‐based mutation analysis in a ‘real‐world’ cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high‐burden mutations, while 52% were low‐burden TP53 mutations. Low‐burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low‐burden TP53 mutation. Patients harbouring low‐burden TP53 mutations had significantly lower time to first treatment compared to patients with wild‐type TP53 . Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low‐burden TP53 mutations. By demonstrating that patients with sole low‐burden TP53 variants represent more than one‐third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting. LA - English DB - MTMT ER - TY - JOUR AU - Kellermayer, Dalma Lucia AU - Tordai, Hedvig AU - Kiss, Balázs AU - Török, György AU - Péter, Dániel M. AU - Sayour, Alex Ali AU - Pólos, Miklós AU - Hartyánszky, István AU - Szilveszter, Bálint AU - Labeit, Siegfried AU - Gángó, Ambrus AU - Bedics, Gábor AU - Bödör, Csaba AU - Radovits, Tamás AU - Merkely, Béla Péter AU - Kellermayer, Miklós TI - Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere JF - JOURNAL OF CLINICAL INVESTIGATION J2 - J CLIN INVEST VL - 134 PY - 2024 IS - 2 PG - 13 SN - 0021-9738 DO - 10.1172/JCI169753 UR - https://m2.mtmt.hu/api/publication/34395421 ID - 34395421 LA - English DB - MTMT ER - TY - JOUR AU - Bátai, Bence AU - Varga, L AU - Weisinger, Júlia AU - Illyés, Gabriella AU - Masszi, András AU - Gergely, Lajos AU - Bátai, Á AU - Gurbity Pálfi, Timea AU - Rejtő, László AU - Plander, Márk AU - Egyed, Miklós AU - Nagy, Z AU - Masszi, Tamás AU - Alpár, Donát AU - Bödör, C TI - HU-LYGEN: A HAZAI DIFFÚZ NAGY B-SEJTES LYMPHOMA MOLEKULÁRIS PROFILOZÁS PROGRAM ELSŐ EREDMÉNYEI JF - MAGYAR BELORVOSI ARCHIVUM J2 - MBA VL - 76 PY - 2023 IS - 5-6 SP - 300 EP - 301 PG - 2 SN - 0133-5464 UR - https://m2.mtmt.hu/api/publication/34558244 ID - 34558244 LA - Hungarian DB - MTMT ER - TY - GEN AU - Dohy, Zsófia AU - Fekete, Bálint András AU - Pozsonyi, Zoltán AU - Csonka, Katalin AU - Nagy, Beáta AU - Fintha, Attila AU - Balla, Dorottya AU - Szabó, Liliána AU - Juhász, Vencel AU - Czimbalmos, Csilla AU - Tóth, Attila AU - Matolcsy, András AU - Merkely, Béla Péter AU - Bödör, Csaba AU - Vágó, Hajnalka TI - Bal kamra hypertrophiát okozó szívizombetegségek szív mágneses rezonanciás és genetikai jellegzetességei. Cardiac magnetic resonance and genetic characteristics of myocardial diseases causing left ventricular hypertrophy TS - Cardiac magnetic resonance and genetic characteristics of myocardial diseases causing left ventricular hypertrophy CY - Balatonfüred PY - 2023 UR - https://m2.mtmt.hu/api/publication/34558230 ID - 34558230 N1 - előadás LA - Hungarian DB - MTMT ER - TY - JOUR AU - Bödör, Csaba AU - Alpár, Donát AU - Bátai, Bence AU - László, Tamás TI - A hazai onkohematológiai kutatás szolgálatában: A Molekuláris Onkohematológia Kutatócsoport első tíz éve JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 67 PY - 2023 IS - 3 SP - 260 EP - 265 PG - 6 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/34452691 ID - 34452691 N1 - Patológiai és Kísérleti Rákkutató Intézet, HCEMM-SE Molekuláris Onkohematológia Kutatócsoport, Semmelweis Egyetem, Budapest, Hungary Belgyógyászati és Hematológiai Klinika, Semmelweis Egyetem, Budapest, Hungary Export Date: 2 January 2024 CODEN: MGONA Correspondence Address: Csaba, B.; Semmelweis Egyetem, Üllői út 26, Hungary; email: bodor.csaba1@semmelweis.hu LA - Hungarian DB - MTMT ER - TY - JOUR AU - Brückner, Edit AU - Bedics, Gábor AU - Reiniger, Lilla AU - Rajnai, Hajnalka AU - Jakab, Zsuzsanna AU - Bödör, Csaba AU - Scheich, Bálint AU - Garami, Miklós TI - Gyermekkori agydaganatok: diagnózis és terápia – komprehenzív genomikai profilozás JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 67 PY - 2023 IS - 4 SP - 315 EP - 320 PG - 6 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/34444932 ID - 34444932 AB - With the advancement of molecular oncology, numerous new opportunities are available for the effective and efficient treatment of patients diagnosed with childhood brain tumors. This includes gene panel analysis aiding personalized treatment used in clinical trials, and the application of targeted therapy independent of tissue type (tumor agnostic therapy). Most personalized therapies inhibit certain kinases. In our review, we present the modern pathological diagnosis of childhood brain tumors, as well as the complex intracellular regulation of signal transduction pathways important from the point of view of clinical practice, and we describe their further targets defined on the basis of pharmacological characteristics of the pathway, based on international and our own results. Despite common mutations affecting kinases, personalized therapy is not available in many types of tumors. Through the example of childhood brain tumors, we demonstrate the expected future therapeutic significance of tyrosine kinases. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Szűcs, Gergő AU - Komáromi, Tamás AU - Matics, Zsombor Zoltán AU - Erdélyi, Tamás AU - Pápay, Judit AU - Kristóf, Katalin AU - Bohács, Anikó AU - Müller, Veronika TI - Pneumocystis diagnosztizálása nem ismert HIV fertőzött betegnél - Esetismertetés JF - MEDICINA THORACALIS (BUDAPEST) J2 - MED THORAC (BP) VL - 76 PY - 2023 IS - 6 SP - 323 EP - 326 PG - 4 SN - 0238-2571 UR - https://m2.mtmt.hu/api/publication/34441434 ID - 34441434 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Varga, Luca Petra AU - Bödör, Csaba AU - Bátai, Bence TI - A Magyar Diffúz Nagy B-sejtes Lymphoma Molekuláris Profilozási Projekt (HU-LyGen): ismertető és első eredmények JF - HEMATOLÓGIA-TRANSZFUZIOLÓGIA J2 - HEMATOLÓGIA-TRANSZFUZIOLÓGIA VL - 56 PY - 2023 IS - 2 SP - 104 EP - 109 PG - 6 SN - 1786-5913 DO - 10.1556/2068.2023.00178 UR - https://m2.mtmt.hu/api/publication/34406243 ID - 34406243 LA - Hungarian DB - MTMT ER -