PhD Scientific Days 2023

Budapest, 22-23 June 2023

Molecular Sciences - Posters K

Molecular Subgroup Classification in Diffuse Large B-cell Lymphoma: First Results of the DLBCL Molecular Profiling Program in Hungary

Luca Varga1, Bence Bátai1, Tamás László1, Gábor Bedics1, Anna Udvari1, Gabriella Illyés2, Péter Attila Király2, János Rottek2, Tamás Schneider2, Szilamér Kovács3, Tamás Szendrei3, Márk Plander3, Soma Sashalmi4, Hermina Sánta4, Árpád Bátai4, Réka Bicskó5, Lajos Gergely5, Bernadett Czibere6, László Rejtő6, Tímea Gurbity-Pálfi7, Zita Borbényi7, Júlia Weisinger8, Zsolt Nagy8, Tamás Masszi8, Zsófia Simon9, Zsombor Ritter10, László Papp11, Erika Tóth12, Réka Mózes13, Ágota Szepesi13, Judit Csomor13, András Matolcsy13, Botond Timár1,13, Donát Alpár1, András Masszi2, Csaba Bödör1

1HCEMM-SE Molecular Oncohematology Research Group, Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest; 2National Institute of Oncology, Department of Hematology and Lymphoma, Budapest; 3 Markusovszky Hospital, Department of Haematology and Haemostasis, Szombathely; 4Fejér Megyei Szent György University Teaching Hospital, Hematology, Székesfehérvár; 5 University of Debrecen, Internal Medicine Clinic, Debrecen; 6Szabolcs-Szatmár-Bereg Megyei Jósa András Teaching Hospital, Department of Hematology, Nyíregyháza; 7University of Szeged, 2nd Department of Internal Medicine, Szeged; 8Semmelweis University, 3rd Internal Medicine, Budapest; 9Szent Borbála Hospital, Department of Haematology, Tatabánya; 10Department of Nuclear Medicine, University of Pécs; 11 Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, Vienna; 12Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest; 13Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest

Text of the abstract

Two-thirds of diffuse large B-cell lymphoma (DLBCL) patients are cured with first-line treatment, but the remaining cases develop poorly treatable relapsed/refractory DLBCL, partly due to the underlying molecular heterogeneity. New classification systems based on multiplex genetic variation could lead to better classification methods, improved risk stratification and therapy selection in the future.
The aim of our research group is to investigate the applicability and prognostic significance of the new molecular classification algorithms in DLBCL in a prospective observational study.
We have developed the 'SU-DLBCL Predictor' gene panel, which allows the analysis of 251 genes, 4 translocation breakpoints (BCL2, BCL6, MYC, PD-L1) and genome-wide copy number variations. During the pilot phase of the project, twenty-four DLBCL patients' diagnostic tissue samples were analysed. After library preparation with a custom SureSelect XTHS2 (Agilent, USA) panel, samples were sequenced on the NextSeq2000 (Illumina, USA) platform and data were evaluated using our own bioinformatics pipeline and the LymphGen classification algorithm.
A median of 19 (min: 9, max: 71) coding variants were identified in the 24 samples analysed, most frequently affecting the KMT2D (42%), CARD11 (42%), HIST1H1E (33%), FAT4 (38%), and TP53 (46%) genes. BCL6 translocation was detected in two patients, while copy number alterations were highly prevalent as amplifications affecting MYC (25%), BCL2 (42%), BCL6 (46%) genes and deletions of the TP53 gene (21%). Based on these abnormalities, 4% of cases were classified as N1, 8% as MCD, 12% as A53, 4% as MCD/A53, 13% as BN2, 8% as EZB, 13% as ST2, and 38% as Other using the LymphGen algorithm.
We are the first in our country to successfully optimize a testing algorithm for the molecular classification of DLBCL, with preliminary results for 24 samples showing overlap with literature data both in terms of variation frequencies and subgroup distribution. Subsequently, patient samples will be analysed using the 'SU-DLBCL Predictor' gene panel.
Funding for this research was provided by NKFIH KDP-1022882, EFOP-3.6.3-VEKOP-16-2017-00009, ÚNKP-21-3-II-SE-24, ÚNKP-22-5-SE-7, ÚNKP-22-3-II-SE-72, H2020-739593, K21_137948, TKP2021-EGA-24, TKP2021-NVA-15, FK20_134253, the MTA Bolyai programme BO/125/22 and Elixir Hungary.