PhD Scientific Days 2026

Poster Session 1.D - Pathological and Oncological Sciences

Phased Variants Reveal Proto-Oncogene Promoter Hypermutation and cfDNA Fragmentation Patterns in DLBCL

Előadó neve

Luca, Varga, MSc

Neptune code

Q40QTZ

Előadó munkahelye

Semmelweis University, Department of Pathology and Experimental Cancer Research, Budapest, Hungary

Előadó telefonszáma

06702892997

Előadó e-mail címe

varga.luca@phd.semmelweis.hu

Az előadás címe

Phased Variants Reveal Proto-Oncogene Promoter Hypermutation and cfDNA Fragmentation Patterns in DLBCL

Szerző(k) neve és munkahelye

Luca Varga^1,2, Péter Király³, Márk Plander⁴, Réka Ráhel Bicskó⁵, Miklós Egyed⁶, Tímea Gurbity Pálfi⁷, Zsófia Zsuzsanna Simon⁸, Gabriella Szepesi^1,2, Nóra Szoboszlai^1,2, Nikolett Szeifer^1,1, Richárd Hanza^1,1, Róbert Horváth⁹, Tamás László^1,9, Tamás Schneider³, Szilamér Kovács⁴, Tamás Szendrei⁴, Hermina Sánta¹⁰, Árpád Bátai¹¹, Árpád Szomor¹⁰, Lajos Gergely⁵, László Rejtő¹², Zita Borbényi⁷, Zsolt Nagy¹³, Masszi Tamás Pál¹³, Erika Tóth³, Réka Mózes⁹, Judit Csomor⁹, András Matolcsy⁹, Donát Alpár^1,14, Botond Timár^1,9,14, András Masszi³, Bence Bátai^1,13,14, Csaba Bödör^1,14

1: Semmelweis University, MTA-SE Momentum Molecular Oncohematology Research Group, Budapest, Hungary
2: Semmelweis University, HCEMM-SE Molecular Oncohematology Research Group, Budapest, Hungary,
3: National Institute of Oncology, Budapest, Hungary
4: Vas Vármegyei Markusovszky Egyetemi Oktató Kórház, Szombathely, Hungary
5: University of Debrecen, Division of Hematology, Department of Internal Medicine, Debrecen, Hungary
6: Kaposi Mór University Teaching Hospital of County Somogy
7: University of Szeged, Szeged, Hungary
8: St. Borbála Hospital, Tatabánya, Hungary
9: Semmelweis University, Department of Pathology and Experimental Cancer Research, Budapest, Hungary
10: Fejér County Szent György University Teaching Hospital, Székesfehérvár, Hungary
11: Central Hospital of Southern Pest, Budapest, Hungary
12: Hospitals of County Szabolcs-Szatmár-Bereg and University Teaching Hospital, Nyíregyháza, Hungary
13: Semmelweis University, Department of Internal Medicine and Haematology, Budapest, Hungary
14: Semmelweis University, HCEMM-SE Molecular Oncohematology Research Group, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session 1.D - Pathological and Oncological Sciences

Language of the presentation

Hungarian

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Introduction
Diffuse large B-cell lymphoma (DLBCL) is a clinically and molecularly heterogeneous disease for which widely applicable patient-stratification tools are still lacking. Circulating tumor DNA (ctDNA) has emerged as a promising approach, yet its utility for molecular characterization and stratification remains incompletely understood. Phased variants (PVs) represent region-specific multiple cis-oriented mutations that may provide additional insight into DLBCL, and improve ctDNA-based stratification.
Aims
Our goal was to characterise a real-world DLBCL cohort to improve our understanding of the disease’s molecular landscape and investigate the applicability of cfDNA for molecular profiling and patient stratification.
Method
138 newly diagnosed DLBCL patients were enrolled in liquid biopsy collection between 2021-2023, of which 116 had corresponding diagnostic FFPE samples available. We performed targeted next generation DNA sequencing using two sequencing panels designed for tissue and cfDNA.
Results
Of the 116 patients with FFPE available, 50.8% was successfully classified into LymphGen subtypes, which increased to 62.9% with the inclusion of cfDNA. Median 112 PVs were identified in FFPE samples. In 86 of the 116 cases, PVs identified from tumor tissue DNA were present in cfDNA as well, with a median of 58.4% of PVs recalled from cfDNA. PVs were most commonly found in IGK, IGHM regions, and the BCL6, BCL2, PIM1, MYC, BCL7A, CXCR4, TMSB4X genes, mostly in 5’UTR or promoter regions. Fragment length analysis revealed ctDNA to be significantly more fragmented to wild-type DNA and total cfDNA. The BCL2 and MYC genes, which showed low PV recall, are characterized by low expression in whole blood and high expression in lymphocytes based on GTEx data. Consequently, high background cfDNA abundance masks ctDNA derived fragmentation signals, impairing phased variant detection in these key driver genes.
Conclusion
CtDNA can carry relevant information on the disease; in our case, LymphGen classification improved with the use of ctDNA variants. We demonstrated that regions with lower cfDNA fragmentation and higher cfDNA amounts have worse PV recall, highlighting caveats to improve in the non-invasive genotyping of DLBCL.
Funding
EKÖP-2024-73, ÚNKP-21-3, K21_137948, H2020-739593, TKP2021-EGA-24, TKP2021-NVA-15, NKFIH KDP-1022882, EFOP-3.6.3, VEKOP-16-2017-00009

University

Semmelweis University

Supervisor

Csaba Bödör

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7425

Start

16:42

End

16:45