INVESTIGATION OF SPATIAL AND TEMPORAL HETEROGENEITY IN THE GENETIC BACKGROUND OF GERMINAL CENTER LYMPHOMAS
Bátai Bence
Pathological Sciences
Dr. Matolcsy András
1st Department of Pathology and Experimental Cancer Research, Lajos Arányi lecture hall
2025-02-06 15:00:00
Experimental Oncology
Dr. Bödör Csaba
Dr. Bödör Csaba
Dr. Wiener Zoltán
Dr. Magyari Ferenc
Dr. Szabó Dóra
Dr. Lotz Gábor
Dr. Pankotai Tibor
Germinal center B cell lymphomas are the most prevalent hematologic malignancies representing diverse lymphoma subtypes. Herein, we aimed to investigate the genetic background of two indolent lymphoma subtypes, primary cutaneous follicle center lymphoma (PCFCL) and follicular lymphoma (FL). Both lymphomas are characterized by slow progression and long term remissions, although relapses develop in the majority of cases and a subset of patients experiences dismal prognosis posing a difficulty in clinical decision making due to the lack of reliable prognostic and predictive biomarkers.
Altogether we investigated 227 biosamples from PCFCL and FL patients in three different studies. We aimed to investigate the role of TNFRSF14 and EZH2 in the pathogenesis of PCFCL and performed genome-wide copy number profiling using low-coverage whole genome sequencing to identify novel diagnostic and prognostic biomarkers in PCFCL. We aimed to investigate the potential of cell-free DNA analysis in FL and leverage its potential to uncover spatial heterogeneity in the disease.
In summary, findings of this study extend our knowledge on the genetic background of PCFCL, that seems to be heterogeneous. We identified for the first time somatic mutations of the TNFRSF14 gene and/or 1p36 loss in the minority of the cases. Based on our results, the copy number profile of PCFCL is only slightly different from that of FL, with the notable exception of the scarcity of 18q amplifications including 18q21.33 which covers the BCL2 locus. This further highlights its potential utility in differential diagnosis of PCFCL and secondary cutaneous infiltration of FL. Our results point to higher genomic instability in patients developing distant disease spread. We further deciphered the role of 2p16.3-p15 amplifications in the disease course of PCFCL, which could be an early prognostic marker in the future for the prediction of distant disease spread. For the first time, we analyzed the temporospatial plasticity of PCFCL investigating serial patient samples highlighting evidence of branching evolutionary processes during disease propagation. Additionally, performing comprehensive genetic profiling on concurrent and serial cell-free DNA and tumor DNA samples in relapsed/refractory FL cases we were able to decipher the spatial compartmentalization of variants including its dynamics leading to disease relapse and investigate the potential utility of circulating tumor DNA analysis in the risk stratification of FL.
