PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session A - Molecular Medicine 1.

Molecular Heterogeneity of Diffuse Large B-cell Lymphoma: A Multi-Centre Real-World Study

Author(s)

Luca Varga1, Gabriella Szepesi1, Tamás László1, Gábor Bedics1, Nóra Szoboszlai1, Richárd Hanza1, Gabriella Illyés2, Péter Attila Király3, János Rottek3, Tamás Schneider3, Szilamér Kovács4, Tamás Szendrei4, Márk Plander4, Soma Sashalmi5, Hermina Sánta5, Árpád Bátai5, Réka Bicskó6, Lajos Gergely6, Bernadett Cibere7, László Rejtő7, Tímea Gurbity-Pálfi8, Zita Borbényi8, Júlia Weisinger9, Zsolt Nagy9, Tamás Masszi9, Zsófia Simon10, Miklós Egyed11, Zsombor Ritter12, Erika Tóth13, Réka Mózes14, Ágota Szepesi14, Judit Csomor14, András Matolcsy14, Botond Tímár14, Donár Alpár1, András Masszi2, Bence Bátai1, Csaba Bödör1
1: HCEMM-SE Molecular Oncohematology Research Group, Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2: National Institute of Oncology, Department of Hematology and Lymphoma, Budapest
3: National Institute of Oncology, Department of Haematology and Lymphoma, Budapest
4: Markusovszky Hospital, Department of Haematology and Haemostasis, Szombathely
5: Fejér Megyei Szent György University Teaching Hospital, Hematology, Székesfehérvár
6: University of Debrecen, Internal Medicine Clinic, Debrecen
7: Szabolcs-Szatmár-Bereg Megyei Jósa András Teaching Hospital, Department of Hematology, Nyíregyháza
8: University of Szeged, 2nd Department of Internal Medicine, Szeged
9: Semmelweis University, 3rd Internal Medicine, Budapest
10: Szent Borbála Hospital, Department of Haematology, Tatabánya
11: Kaposi Mór Teaching Hospital, Department of Haematology, Kaposvár
12: Department of Nuclear Medicine, University of Pécs
13: Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest
14: Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest

Text of the abstract

Introduction: Two-thirds of diffuse large B-cell lymphoma (DLBCL) patients are cured with first-line treatment, however, one-third still develop relapsed/refractory DLBCL with inferior prognosis. This is partly due to the underlying molecular heterogeneity of the disease. In a multi-centre study, our research team is collecting tissue and follow-up liquid biopsy materials from a total of 124 newly diagnosed DLBCL patients from nine haematology centres in Hungary, starting from September 2022.

Aims: We aim to assess the utility of currently available molecular classification systems on a "real-world" cohort.

Method: We have created the proprietary 'SU-DLBCL Predictor' gene panel, which allows the analysis of 251 genes, 4 translocation breakpoints (BCL2, BCL6, MYC, PD-L1) and copy number variations genome-wide. Eighty-three tissue samples from patients with DLBCL at diagnosis were analysed using this panel. After library preparation with a custom SureSelect XTHS2 (Agilent, USA) panel, samples were sequenced on NextSeq2000 (Illumina, USA) platform and data were evaluated using our bioinformatics pipeline, the LymphGen classification algorithm and R statistical software.

Results: In the 83 samples analysed, the LymphGen algorithm identified 10 ST2 (12%), 8 EZB (9.5%), 8 BN2 (9.5%), 6 MCD (7%), 5 A53 (6%), 2 N1 (2%), 3 composite (4%) and 41 Other (50%) cases. Mutations were most frequently identified in the KMT2D (48%), PABPC1 (39%), HIST1H1E (28%), MYD88 (27%), and TP53 (27%) genes, with copy number gains most frequently involving the BCL2 (31%), BCL6 (27%), and SOCS1 (25%) genes. 17p deletions were detected in 7 samples (8%).

Results: We were the first in Hungary to successfully optimize a test algorithm for the classification of DLBCL. Our preliminary results for 83 samples show a large overlap with the literature both in terms of variation frequency and subgroup distribution.

Funding: The research was funded by the NRDIH 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.