Mutational profile of primary breast diffuse large B-cell lymphoma

Abstract

Primary breast lymphoma is a rare form of extra-nodal lymphoid neoplasm. The most common histological type is the diffuse large B-cell lymphoma, which represents 60–80% of all the cases. Our study analyzes the mutational profile of the primary lymphoma of the breast through targeted massive sequencing with a panel of 38 genes in a group of 17 patients with primary breast diffuse large B-cell lymphoma. Seventy-point-five percent of the patients presented with stage IE and 29.5% with stage IIE. 44% of the cases correspond to lymphomas with germinal center phenotype and 33.3% to activated B-cell. The genes with a higher mutational frequency include PIM1 (in 50% of the analyzed samples), MYD88 (39%), CD79B, PRDM1 and CARD11 (17%), KMT2D, TNFIAP3 and CREBBP (11%). The profile of mutant genes involves mostly the NFκB signaling pathway. The high frequency of mutations in PIM1 compared with other lymphomas may have implications in the clinical presentation and evolution of this type of lymphoma.

Molecular Heterogeneity in Localized Diffuse Large B-Cell Lymphoma

“…With a high mutation rate in DLBCL, the functions of MPEG1 mutations need to be investigated further. In concordance with previous reports in DLBCL ( 11 , 13 , 30 ), MYD88 and PIM1 mutations were frequent in localized DLBCL patients with breast involvement while rare in those with GI tract involvement. As for oncogenic cascades, the TGF-β signaling pathway has been reported to be associated with extranodal involvement in DLBCL ( 31 , 32 ).…”

Influence of oncogenic mutations and tumor microenvironment alterations on extranodal invasion in diffuse large B‐cell lymphoma

“…[41][42][43] Of note, a series of gene mutations co-occurred with MYD88, including PIM1, TBL1XR1, BTG1, MPEG1, and PRDM1, all of which presented high frequency in the MCD subtype defined by Schmitz et al, contributing to NF-κB activation in a B cell receptor-dependent manner. 8 High frequencies of PIM1 44 and TBL1XR1 45 mutations were also observed in breast and testis lymphoma, respectively. These findings confirmed the experimental data showing that MYD88 L265P alone is insufficient to drive malignant transformation in B cells and may cooperatively induce lymphoma with other genetic events.…”

Immune polychemotherapy regimen choice in B-cell non-Hodgkin lymphoma of high and low malignancy based on the identification of the mutational c-myc and BCL 2 genes

“…In this regard, in all planned scientific studies, the main purpose is to study the effectiveness of the molecular genetic profile of a tumour of the lymphoid system and thereby improve and implement innovative approaches in the diagnosis and treatment prognosis. [16][17][18][19][20] The results of a study of the molecular genetic features of BCL revealed the presence of the c-myc and BCL 2 gene in 9 patients and 80 co-expressions and the use of high-dose immune chemotherapy allowed to identify several genetic subtypes of this disease that differ in the course and response to therapy. The use of high-dose PCT followed by HSC transplantation in patients with co-expression of the cmyc and BCL 2 gene showed a high efficiency of the therapy and justified our prognosis of treatment effectiveness.…”