Genomic landscape of para-skeletal and extramedullary plasmacytomas in multiple myeloma patients

• Authors: ŠTORK Martin; KOTAŠKOVÁ Jana; ONDROUŠKOVÁ Eva; MAREČKOVÁ Andrea; MENŠÍKOVÁ Klára; SENDLEROVÁ Nela; BOICHUK Ivanna; BILČÍKOVÁ Michaela; MAYEROVÁ Johana; RŮŽIČKOVÁ Tereza; KNECHTOVÁ Zdeňka; JELÍNKOVÁ Zuzana; KRTIČKA Milan; NEKUDA Vladimír; ROHAN Tomáš; BORSKÝ Marek; HRABČÁKOVÁ Viera; ŠEVČÍKOVÁ Sabina; JAROŠOVÁ Marie; POUR Luděk
• Year of publication: 2025
• Type: Conference abstract
• MU Faculty or unit: Faculty of Medicine
• Description: Extramedullary disease (EMM) in multiple myeloma (MM) represents an aggressive, treatment-resistant subtype with poor prognosis. It manifests as para-skeletal plasmacytomas (PS) originating from osteolytic lesions or as extramedullary plasmacytomas (EMD) developing in soft tissues without bone involvement. We performed a comprehensive molecular analysis of 40 EMM tissue samples, including targeted next-generation sequencing (NGS), interphase FISH, and flow cytometry, with parallel analyses of 15 matched bone marrow plasma cell (BMPC) samples. EMD plasmacytomas were characterized by frequent 1p deletions, rare NOTCH1/2 mutations, and low NCAM (CD56) expression, whereas PS plasmacytomas showed a higher prevalence of KRAS mutations. Comparative analysis between EMM plasma cells and BMPCs revealed newly acquired MAPK pathway mutations and biallelic inactivation of tumor suppressor genes in a subset of cases. These results demonstrate distinct genomic and phenotypic profiles of EMD and PS subtypes, underscoring the molecular heterogeneity of EMM and its potential relevance for targeted therapeutic strategies.