Dissertation committee:
Μελέτιος-Αθανασιος Δημόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Ευάγγελος Τέρπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία-Χριστινα Κυρτσωνη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ευστάθιος Καστρίτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαριάννα Πολίτου, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Φλώρα Ζαγουρή, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Γαβριατοπούλου, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Liquid biopsy is being integrated into cancer diagnostics with profound therapeutic implications. However, its role in Waldenström’s Macroglobulinemia (WM) and IgM monoclonal gammopathies is still unclear. In this study, we evaluated the role of peripheral blood cell-free DNA (cfDNA) in characterizing the mutational status of MYD88 and CXCR4 of patients with IgM monoclonal gammopathies. Paired bone marrow tumor DNA (tDNA) and peripheral blood cfDNA samples from 207 patients (40 MGUS, 47 with WM in remission, 103 with smoldering WM, newly diagnosed or relapsed WM) and 10 controls with non-IgM monoclonal gammopathies were analyzed. Regarding MYD88L265P mutation, 150 patients had paired tDNA and cfDNA informative samples. The overall concordance rate was 97% (145/150) (p<0.001). Similar concordance rates were detected among disease subgroups. For CXCR4 mutations, 131 patients had paired informative tDNA and cfDNA samples. The overall concordance rate was 84% (110/131) (p<0.001). The corresponding concordance rates among disease subgroups were similar. All controls were wild-type for MYD88 and CXCR4. In conclusion, peripheral blood cfDNA is a useful, minimally invasive, cost effective and time-effective tool for the identification of the presence of MYD88 and CXCR4 mutations in patients with IgM monoclonal gammopathies avoiding unnecessary bone marrow assessment.
Keywords:
Liquid biopsy, Cell free DNA, Waldenstrom macroglobulinemia, MYD88, CXCR4
