PhD Scientific Days 2026

Poster Session 2.E - Pathological and Oncological Sciences

Genetic Aberrations in Multiple Myeloma and Myeloma Cutis

Name of the presenter

Kardos, Balázs

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research

Authors

Balázs Kardos¹, Zsófia Urbán², Róbert Horváth³, Tímár Botond², Anna Bekő², Fruzsina Szél⁴, Ádám Wiedemann⁴, Gábor Barna², Gergő Papp², Ildikó Istenes⁵, Beáta Margit Deák⁶, András Masszi⁶, Zsuzsanna Szemlaky⁷, Péter Rajnics⁸, Márk Plander⁹, Tamás Masszi⁴, András Matolcsy², Gábor Mikala⁴, Gergely Varga⁴, Csaba Bödör²
1: Department of Pathology and Experimental Cancer Research
2: MTA-SE Lendület Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University
3: Department of Laboratory Medicine, Semmelweis University
4: Department of Internal Medicine and Haematology, Semmelweis University
5: Department of Internal Medicine and Oncology, Semmelweis University
6: National Institute of Oncology
7: National Institute for Infectology and Haematology, South Pest Central Hospital
8: Teaching Hospital Mór Kaposi
9: Teaching Hospital Markusovszky

Text of the abstract

Introduction
Multiple myeloma (MM) is a clonal plasma cell disorder characterized by the proliferation of long-lived plasma cells in the bone marrow. As the disease progresses, extramedullary manifestations may appear, characterized by the presence of abnormal plasma cells outside the bone marrow. One subtype of extramedullary multiple myeloma is myeloma cutis (MC), which is a very rare manifestation of the disease.

Aims
We aimed to evaluate the applicability of OGM (Optical Genome Mapping) and sWGS (shallow Whole-Genome Sequencing) in MM and to systematically define the landscape of structural and copy number alterations – including previously undescribed events and genomic complexity patterns – and to identify these alterations in extramedullary manifestations as well.

Methods
Diagnostic bone marrow aspirates (BMAs) from 80 patients with MM at the time of diagnosis and during relapse, and MC skin biopsies from 25 patients were collected at relapse. All 80 MM patients were analyzed by OGM, and 25 MC patients were analyzed with sWGS. The resulting genome maps were used to evaluate the genomic profile of the samples and to identify biologically or clinically relevant alterations.

Result
We found translocations involving the immunoglobulin heavy chain (IGH) region at Chr14q32.33. Additionally, novel translocations affecting the IGH region were identified in 7 patients. Simultaneous IGH translocations involving different partner chromosomes were identified in 9 cases. These findings indicate the presence of complex IGH rearrangement patterns within individual genomes. The presence of 17p deletion was demonstrated in 20 patients. Deletions involving chromosome 1p were identified in 26 cases and frequently affected more than one subregion within the same genome. Gain of 1q21 was observed in 30 cases, with 8 patients demonstrating high-level amplification. Chromothripsis and chromoplexy were identified in 12 and 5 patients.

Conclusion
Application of OGM and sWGS provided a high-resolution characterization of the genomic landscape in MM and its extramedullar manifestations, revealing novel, previously unreported IGH translocations, concurrent IGH rearrangements, and regionally complex 1p deletions, while accurately identifying 1q21 gain and amplification.

Funding
LP2024-3, K21_137948, H2020-739593, TKP2021-EGA-24, TKP2021-NVA-15, EKÖP-2025-559, ELIXIR Hungary