TY - JOUR AU - Sztupinszki, Zsófia AU - Diossy, Miklos AU - Borcsok, Judit AU - Prosz, Aurel AU - Cornelius, Nanna AU - Kjeldsen, Maj K. AU - Mirza, Mansoor R. AU - Szállási, Zoltán TI - Comparative Assessment of Diagnostic Homologous Recombination Deficiency-Associated Mutational Signatures in Ovarian Cancer JF - CLINICAL CANCER RESEARCH J2 - CLIN CANCER RES VL - 27 PY - 2021 IS - 20 SP - 5681 EP - 5687 PG - 7 SN - 1078-0432 DO - 10.1158/1078-0432.CCR-21-0981 UR - https://m2.mtmt.hu/api/publication/32474433 ID - 32474433 N1 - Funding Agency and Grant Number: Research and Technology Innovation Fund [KTIA_NAP_13-2014-0021, 2017-1.2.1-NKP-2017-00002]; Breast Cancer Research Foundation [BCRF-20-159]; Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant [NNF15OC0016584]; Kraeftens Bekaempelses Videnskabelige Udvalg [R281A16566]; Det Frie Forskningsra~ d, Sundhed og Sygdom [7016-00345B]; Department of Defense through the Prostate Cancer Research ProgramUnited States Department of Defense [W81XWH-18-2-0056]; Basser Foundation; Velux Foundation [00018310] Funding text: This work was supported by the Research and Technology Innovation Fund (KTIA_NAP_13-2014-0021 and 2017-1.2.1-NKP-2017-00002, to Z. Szallasi), Breast Cancer Research Foundation (BCRF-20-159, to Z. Szallasi), the Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant (NNF15OC0016584, to Z. Szallasi), Kraeftens Bekaempelses Videnskabelige Udvalg (award number R281A16566, to Z. Szallasi), Det Frie Forskningsra~ d, Sundhed og Sygdom (award number, 7016-00345B, to Z. Szallasi), Department of Defense through the Prostate Cancer Research Program (award number W81XWH-18-2-0056, to Z. Szallasi), and Basser Foundation (to Z. Szallasi). Z. Sztupinszki and J. Borcsok were supported by Velux Foundation 00018310 grant. The results shown here are based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/and the International Cancer Genome Consortium (ICGC): https://icgc.org/. AB - Purpose: Homologous recombination (HR) deficiency (HRD) is one of the key determinants of PARP inhibitor response in ovarian cancer, and its accurate detection in tumor biopsies is expected to improve the efficacy of this therapy. Because HRD induces a wide array of genomic aberrations, mutational signatures may serve as a companion diagnostic to identify PARP inhibitor-responsive cases. Experimental Design: From the The Cancer Genome Atlas (TCGA) whole-exome sequencing (WES) data, we extracted different types of mutational signature-based HRD measures, such as the HRD score, genome-wide LOH, and HRDetect trained on ovarian and breast cancer-specific sequencing data. We compared their performance to identify BRCA1/2-deficient cases in the TCGA ovarian cancer cohort and predict survival benefit in platinum-treated, BRCA1/2 wild-type ovarian cancer. Results: We found that the HRD score, which is based on large chromosomal alterations alone, performed similarly well to an ovarian cancer-specific HRDetect, which incorporates mutations on a finer scale as well (AUC = 0.823 vs. AUC = 0.837). In an independent cohort these two methods were equally accurate predicting long- term survival after platinum treatment (AUC = 0.787 vs. AUC = 0.823). We also found that HRDetect trained on ovarian cancer was more accurate than HRDetect trained on breast cancer data (AUC = 0.837 vs. AUC = 0.795; P = 0.0072). Conclusions: When WES data are available, methods that quantify only large chromosomal alterations such as the HRD score and HRDetect that captures a wider array of HRD-induced genomic aberrations are equally efficient identifying HRD ovarian cancer cases. LA - English DB - MTMT ER - TY - JOUR AU - Diossy, Miklos AU - Sztupinszki, Zsófia AU - Borcsok, Judit AU - Krzystanek, Marcin AU - Tisza, Viktoria AU - Spisák, Sándor AU - Rusz, Orsolya AU - Tímár, József AU - Csabai, István AU - Fillinger, János AU - Moldvay, Judit AU - Pedersen, Anders Gorm AU - Szüts, Dávid AU - Szállási, Zoltán TI - A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures JF - NPJ PRECISION ONCOLOGY J2 - NPJ PRECIS ONCOL VL - 5 PY - 2021 IS - 1 PG - 8 SN - 2397-768X DO - 10.1038/s41698-021-00199-8 UR - https://m2.mtmt.hu/api/publication/32076418 ID - 32076418 N1 - Funding Agency and Grant Number: Research and Technology Innovation Fund [KTIA_NAP_13-2014-0021]; Breast Cancer Research Foundation [BCRF-17-156]; Kraeftens Bekaempelse [R281-A16566]; Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant [NNF15OC0016584]; Department of Defense through the Prostate Cancer Research ProgramUnited States Department of Defense [W81XWH-18-2-0056]; Det Frie Forskningsrad Sundhed og Sygdom [7016-00345B]; Velux FoundationVelux Fonden [00018310] Funding text: The results shown here are based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.This work was supported by the Research and Technology Innovation Fund (KTIA_NAP_13-2014-0021 to Z.Szallasi.), Breast Cancer Research Foundation (BCRF-17-156 to Z.Szallasi.), Kraeftens Bekaempelse (R281-A16566 to Z.Szallasi.), the Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant (NNF15OC0016584 to Z.Szallasi. and I.C.), Department of Defense through the Prostate Cancer Research Program (W81XWH-18-2-0056 to Z.Szallasi.), Det Frie Forskningsrad Sundhed og Sygdom (7016-00345B to Z.Szallasi.), and the Velux Foundation (00018310 to Z.Sztupinszki. and J.B.). LA - English DB - MTMT ER - TY - JOUR AU - Diossy, Miklos AU - Sztupinszki, Zsófia AU - Krzystanek, Marcin AU - Borcsok, Judit AU - Eklund, Aron C AU - Csabai, István AU - Pedersen, Anders Gorm AU - Szállási, Zoltán TI - Strand Orientation Bias Detector to determine the probability of FFPE sequencing artifacts. JF - BRIEFINGS IN BIOINFORMATICS J2 - BRIEF BIOINFORM VL - 22 PY - 2021 IS - 6 SP - 1 EP - 10 PG - 10 SN - 1467-5463 DO - 10.1093/bib/bbab186 UR - https://m2.mtmt.hu/api/publication/32034134 ID - 32034134 AB - Formalin-fixed paraffin-embedded tissue, the most common tissue specimen stored in clinical practice, presents challenges in the analysis due to formalin-induced artifacts. Here, we present Strand Orientation Bias Detector (SOBDetector), a flexible computational platform compatible with all the common somatic SNV-calling pipelines, designed to assess the probability whether a given detected mutation is an artifact. The underlying predictor mechanism is based on the posterior distribution of a Bayesian logistic regression model trained on The Cancer Genome Atlas whole exomes. SOBDetector is a freely available cross-platform program, implemented in Java 1.8. LA - English DB - MTMT ER - TY - JOUR AU - Börcsök, Judit AU - Sztupinszki, Zsófia AU - Bekele, Raie AU - Gao, Sizhi P AU - Diossy, Miklos AU - Samant, Amruta S AU - Dillon, Kasia M AU - Tisza, Viktoria AU - Spisák, Sándor AU - Rusz, Orsolya AU - Csabai, Istvan AU - Pappot, Helle AU - Frazier, Zoe J AU - Konieczkowski, David J AU - Liu, David AU - Vasani, Naresh AU - Rodrigues, James A AU - Solit, David B AU - Hoffman-Censits, Jean H AU - Plimack, Elizabeth R. AU - Rosenberg, Jonathan E AU - Lazaro, Jean-Bernard AU - Taplin, Mary-Ellen AU - Iyer, Gopa AU - Brunak, Søren AU - Lózsa, Rita Bernadett AU - Van Allen, Eliezer M AU - Szüts, Dávid AU - Mouw, Kent W AU - Szállási, Zoltán TI - Identification of a Synthetic Lethal Relationship between Nucleotide Excision Repair Deficiency and Irofulven Sensitivity in Urothelial Cancer JF - CLINICAL CANCER RESEARCH J2 - CLIN CANCER RES VL - 27 PY - 2021 IS - 7 SP - 2011 EP - 2022 PG - 12 SN - 1078-0432 DO - 10.1158/1078-0432.CCR-20-3316 UR - https://m2.mtmt.hu/api/publication/31781512 ID - 31781512 N1 - Funding Agency and Grant Number: Research and Technology Innovation Fund [KTIA_NAP_13-2014-0021]; Breast Cancer Research Foundation [BCRF-17-156]; Novo Nordisk Foundation Interdisciplinary Synergy Programme grant [NNF15OC0016584]; Novo Nordisk Foundation Center for Protein Research core grant [NNF14CC0001]; Department of Defense through the Prostate Cancer Research ProgramUnited States Department of Defense [W81XWH-18-2-0056]; Det Frie Forskningsrad Sundhed og Sygdom [7016-00345]; Burroughs-Wellcome FundBurroughs Wellcome Fund; Dana-Farber Whole Foods Golf Fund; NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [5K08CA219504, R01 CA227388]; Fox Chase Cancer Center NCI Core grant [P30CA00692]; Velux FoundationsVelux Fonden [00018310]; Department of DefenseUnited States Department of Defense [CA160312P2] Funding text: Results shown here are based, in part, from data generated by The Cancer Genome Atlas Research Network: http://cancergenome.nih.gov/and the International Cancer Genome Consortium: https://icgc.org/.This work was supported by the Research and Technology Innovation Fund (KTIA_NAP_13-2014-0021 to Z. Szallasi), Breast Cancer Research Foundation (BCRF-17-156 to Z. Szallasi), the Novo Nordisk Foundation Interdisciplinary Synergy Programme grant (NNF15OC0016584 to Z. Szallasi), the Novo Nordisk Foundation Center for Protein Research core grant (NNF14CC0001 to S. Brunak), Department of Defense through the Prostate Cancer Research Program (W81XWH-18-2-0056 to Z. Szallasi), Det Frie Forskningsrad Sundhed og Sygdom (7016-00345B to Z. Szallasi), Burroughs-Wellcome Fund (to K. W. Mouw), Dana-Farber Whole Foods Golf Fund (to M.-E. Taplin), the NCI (5K08CA219504 to K.W. Mouw and R01 CA227388 to E.M. Van Allen), Fox Chase Cancer Center NCI Core grant (P30CA00692 to E. R. Plimack), the Velux Foundations (00018310 to Z. Sztupinszki and J. Borcsok) and Department of Defense CA160312P2 (to J.E. Rosenberg and E.M. Van Allen). LA - English DB - MTMT ER - TY - JOUR AU - Duan, Haohui AU - Mansour, Sarah AU - Reed, Rachel AU - Gillis, Margaret K. AU - Parent, Benjamin AU - Liu, Ben AU - Sztupinszki, Zsófia AU - Birkbak, Nicolai AU - Szállási, Zoltán AU - Elia, Andrew E. H. AU - Garber, Judy E. AU - Pathania, Shailja TI - E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells JF - JOURNAL OF CELL BIOLOGY J2 - J CELL BIOL VL - 219 PY - 2020 IS - 6 PG - 27 SN - 0021-9525 DO - 10.1083/jcb.201908192 UR - https://m2.mtmt.hu/api/publication/31518657 ID - 31518657 AB - BRCA1/2 help maintain genomic integrity by stabilizing stalled forks. Here, we identify the E3 ligase RFWD3 as an essential modulator of stalled fork stability in BRCA2-deficient cells and show that codepletion of RFWD3 rescues fork degradation, collapse, and cell sensitivity upon replication stress. Stalled forks in BRCA2-deficient cells accumulate phosphorylated and ubiquitinated replication protein A (ubq-pRPA), the latter of which is mediated by RFWD3. Generation of this intermediate requires SMARCAL1, suggesting that it depends on stalled fork reversal. We show that in BRCA2-deficient cells, rescuing fork degradation might not be sufficient to ensure fork repair. Depleting MRE11 in BRCA2-deficient cells does block fork degradation, but it does not prevent fork collapse and cell sensitivity in the presence of replication stress. No such ubq-pRPA intermediate is formed in BRCA1-deficient cells, and our results suggest that BRCA1 may function upstream of BRCA2 in the stalled fork repair pathway. Collectively, our data uncover a novel mechanism by which RFWD3 destabilizes forks in BRCA2-deficient cells. LA - English DB - MTMT ER - TY - JOUR AU - Fluckiger, Aurélie AU - Daillère, Romain AU - Sassi, Mohamed AU - Sixt, Barbara Susanne AU - Liu, Peng AU - Loos, Friedemann AU - Richard, Corentin AU - Rabu, Catherine AU - Alou, Maryam Tidjani AU - Goubet, Anne-Gaëlle AU - Lemaitre, Fabien AU - Ferrere, Gladys AU - Derosa, Lisa AU - Duong, Connie P M AU - Messaoudene, Meriem AU - Gagné, Andréanne AU - Joubert, Philippe AU - De Sordi, Luisa AU - Debarbieux, Laurent AU - Simon, Sylvain AU - Scarlata, Clara-Maria AU - Ayyoub, Maha AU - Palermo, Belinda AU - Facciolo, Francesco AU - Boidot, Romain AU - Wheeler, Richard AU - Boneca, Ivo Gomperts AU - Sztupinszki, Zsófia AU - Papp, Krisztián AU - Csabai, István AU - Pasolli, Edoardo AU - Segata, Nicola AU - Lopez-Otin, Carlos AU - Szállási, Zoltán AU - Andre, Fabrice AU - Iebba, Valerio AU - Quiniou, Valentin AU - Klatzmann, David AU - Boukhalil, Jacques AU - Khelaifia, Saber AU - Raoult, Didier AU - Albiges, Laurence AU - Escudier, Bernard AU - Eggermont, Alexander AU - Mami-Chouaib, Fathia AU - Nistico, Paola AU - Ghiringhelli, François AU - Routy, Bertrand AU - Labarrière, Nathalie AU - Cattoir, Vincent AU - Kroemer, Guido AU - Zitvogel, Laurence TI - Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage. JF - SCIENCE J2 - SCIENCE VL - 369 PY - 2020 IS - 6506 SP - 936 EP - 942 PG - 7 SN - 0036-8075 DO - 10.1126/science.aax0701 UR - https://m2.mtmt.hu/api/publication/31409077 ID - 31409077 AB - Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Enterococcus hirae Mice bearing E. hirae harboring this prophage mounted a TMP-specific H-2Kb-restricted CD8+ T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice. In renal and lung cancer patients, the presence of the enterococcal prophage in stools and expression of a TMP-cross-reactive antigen by tumors correlated with long-term benefit of PD-1 blockade therapy. In melanoma patients, T cell clones recognizing naturally processed cancer antigens that are cross-reactive with microbial peptides were detected. LA - English DB - MTMT ER - TY - JOUR AU - Sztupinszki, Zsófia AU - Diossy, Miklos AU - Krzystanek, Marcin AU - Börcsök, Judit AU - Pomerantz, Mark M AU - Tisza, Viktoria AU - Spisák, Sándor AU - Rusz, Orsolya AU - Csabai, István AU - Freedman, Matthew L AU - Szállási, Zoltán TI - Detection of molecular signatures of homologous recombination deficiency in prostate cancer with or without BRCA1/2 mutations JF - CLINICAL CANCER RESEARCH J2 - CLIN CANCER RES VL - 26 PY - 2020 IS - 11 SP - 2673 EP - 2680 PG - 8 SN - 1078-0432 DO - 10.1158/1078-0432.CCR-19-2135 UR - https://m2.mtmt.hu/api/publication/31194960 ID - 31194960 N1 - Z. Sztupinszki and M. Diossy contributed equally to the article LA - English DB - MTMT ER - TY - JOUR AU - Diossy, M AU - Reiniger, Lilla AU - Sztupinszki, Zsófia AU - Krzystanek, M AU - Timms, K M AU - Neff, C AU - Solimeno, C AU - Pruss, D AU - Eklund, A C AU - Tóth, Erika AU - Kiss, O AU - Rusz, O AU - Cserni, G AU - Zombori, Tamás AU - Székely, Borbála AU - Kulka, Janina AU - Tímár, J AU - Csabai, István AU - Szállási, Zoltán TI - Corrigendum to: Breast cancer brain metastases show increased levels of genomic aberration-based homologous recombination deficiency scores relative to their corresponding primary tumors JF - ANNALS OF ONCOLOGY J2 - ANN ONCOL VL - 30 PY - 2019 IS - 8 SP - 1406 EP - 1406 PG - 1 SN - 0923-7534 DO - 10.1093/annonc/mdz081 UR - https://m2.mtmt.hu/api/publication/30625426 ID - 30625426 LA - English DB - MTMT ER - TY - JOUR AU - Németh, Eszter AU - Krzystanek, Marcin AU - Reiniger, Lilla AU - Ribli, Dezső AU - Pipek, Orsolya Anna AU - Sztupinszki, Zsófia AU - Glasz, Tibor AU - Csabai, István AU - Moldvay, Judit AU - Szállási, Zoltán AU - Szüts, Dávid TI - The genomic imprint of cancer therapies helps timing the formation of metastases JF - INTERNATIONAL JOURNAL OF CANCER J2 - INT J CANCER VL - 145 PY - 2019 IS - 3 SP - 694 EP - 704 PG - 11 SN - 0020-7136 DO - 10.1002/ijc.32159 UR - https://m2.mtmt.hu/api/publication/30417572 ID - 30417572 LA - English DB - MTMT ER - TY - THES AU - Sztupinszki, Zsófia TI - Szolid tumorok terápia szempontjából jelentős klinikai alcsoportokba való sorolása génexpressziós adatok alapján PY - 2018 DO - 10.14753/SE.2018.2114 UR - https://m2.mtmt.hu/api/publication/30643683 ID - 30643683 LA - Hungarian DB - MTMT ER -