MYD88 p.L265P and CD79B p.Y196C/H mutations were analyzed in diffuse large B-cell lymphoma (DLBCL) patients whose tumor samples were available (N = 29).
High frequencies of the hotspot <i>MYD88</i>(L265P) mutation are observed in extranodal diffuse large B-cell lymphoma and Waldenström macroglobulinemia, thereby demonstrating this mutation's potential as a disease marker.
MYD88 L265P is the most common mutation in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and one of the most frequent in poor-prognosis subtypes of diffuse large B-cell lymphoma (DLBCL).
<i>Results</i>: MYD88 L265P mutations were detected in 22 of 29 samples from 14 patients with diffuse large B-cell lymphomas and one patient with lymphoplasmacytoid lymphoma.
Recent studies demonstrated that in the activated B cell subtype of diffuse large B cell lymphoma (DLBCL), approximately one-third of the patients harbored somatically acquired MyD88 L265P mutation in their lymphomas.
A missense mutation (L265P) changing leucine at position 265 to proline in MYD88 is found in ∼90% of Waldenström macroglobulinemia (WM) cases and in significant portions of activated B-cell diffuse large B-cell lymphomas and IgM monoclonal gammopathy of undetermined significance.
Primary DLBCL in sanctuary sites (DLBCL-SS) also demonstrates these features, and >70% of patients harbor myeloid differentiation primary response 88 (MYD88) (L265P) and CD79B mutations.
Finally, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated <i>CD79B</i> mutations significantly improved the survival of MYD88 L265P-mutant ABC DLBCL in our cohort.<b>Conclusions:</b> This study highlights the relative heterogeneity of <i>MYD88</i>-mutant DLBCL, adding to the field's knowledge of the theranostic importance of <i>MYD88</i> mutations, but also of associated alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy.<i></i>.
We identified the MYD88 L265P somatic variant in cases with WM (39/42), MGUS (8/18), NHL (14/41, including 4/13 diffuse large B cell lymphoma (DLBCL), 1/8 mucosa-associated lymphoid tissue, 3/6 splenic marginal zone lymphoma (SMZL), 1/4 chronic lymphocytic leukemia, 2/3 nodal marginal zone lymphoma (NMZL), 1/2 mantle cell lymphoma, 1 Burkitt lymphoma, and 1 B cell NHL that could not be classified), primary AL (2/2), and IgM-PN (1/1).
Also, MYD88L265P had little involvement in GI DLBCL compared with other extranodal DLBCLs, suggesting that its pathogenesis might be different from that of organs with a high frequency of MYD88 L265P.
Heterozygous MYD88 L265P mutations were identified in 11 (9.2%) DLBCL cases, all of which were diagnosed as non-germinal-center B cell (non-GCB) DLBCL.