Mutational frequencies of <i>CD79B</i> and <i>MYD88</i> vary greatly between primary testicular DLBCL and gastrointestinal DLBCL

Frick, Mareike; Bettstetter, Marcus; Bertz, Simone; Schwarz-Furlan, Stephan; Hartmann, Arndt; Richter, Thomas; Lenze, Dido; Hummel, Michael; Dreyling, Martin; Lenz, Georg; Gäumann, Andreas

doi:10.1080/10428194.2017.1370546

Cited by 16 publications

(22 citation statements)

References 15 publications

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“…Consistent with our study, the MSK-IMPACT Clinical Sequencing Cohort reported a mutation frequency of 37.84% for KMT2D in 74 patients with DLBCL, but KMT2D mutation was not detected in 5 cases of GI-DLBCL (18). Frick et al (9) and Nagakita et al (31) reported that MYD88 mutations exhibited less involvement in GI-DLBCL than in nodal DLBCL and other extranodal DLBCLs. In our previous study, the EZH2 Y641 mutation was successfully detected in one of 94 patients with GI-DLBCL (including 33 patients with GCB-DLBCL and 61 patients with non-GCB-DLBCL) by Sanger sequencing, and the mutation frequency was significantly reduced compared with that in non-gastrointestinal DLBCL (16).…”

Section: Discussionsupporting

confidence: 90%

“…However, MYD88 and CARD11 mutations were not detected in 25 patients with GI-DLBCL. Intriguingly, although CD79B mutations were detected in two patients (8%) with GI-DLBCL, the frequency was significantly reduced compared with that in the testes (18.9∼71.4%) (9,11,37) and central nervous system (31.6∼61.1%) DLBCLs (36,38,39). Moreover, only one case had an activating mutation at p.Y197 of CD79B gene (Supplementary Table 2).…”

Section: Discussionmentioning

confidence: 96%

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Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Chai

Chen

et al. 2021

Front. Oncol.

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Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79–382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB, and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D, and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA, and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 96%

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Chai

Chen

et al. 2021

Front. Oncol.

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“…The MYD88 mutation in patients with ABC-DLBCL and PCNSL is of great significance to evaluate the prognosis of dlBcl, suggesting that this is a potential therapeutic target with immunotherapies. it has previously been reported that the MYd88 mutation rate of primary testicular diffuse large B cell lymphoma (PT-dlBcl) is 68%, and associated with a poor survival (21,48,49). Mutations were detected in three patients with PT-dlBcl (2/3) in the present study.…”

Section: Myd88 Mutation Chi-square Test Myd88 Expression Chi-square Tsupporting

confidence: 54%

Prognostic value of MYD88 L265P mutation in diffuse large B cell lymphoma via droplet digital PCR

Niu

Nuerlan

et al. 2020

Mol Med Rep

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To assess the prevalence and prognostic value of myeloid differentiation factor 88 (MYd88) expression and mutational status in diffuse large B cell lymphoma (dlBcl), a total cohort of 100 patients with dlBcl were studied using immunohistochemistry (iHc) and droplet digital polymerase chain reaction (ddPcr), and the association between MYd88 expression and clinicopathological parameters was analyzed. overall, the positive expression rate of MYd88 protein was 38% and the gene mutation rate was 29%. The positive expression and mutation rates were the highest in the primary central nervous system lymphomas (58.33 and 66.67%, respectively). The coincidence rate of the results of MYd88 expression between iHc and ddPcr results was 73% (73/100). univariate survival analysis showed that age (≥60 years old), high neutrophil/lymphocyte count ratio, low lymphocyte count, c-Myc ≥40%, positive MYd88 protein expression, and gene mutation were associated with poorer prognosis rates. Multivariate survival analysis revealed that MYd88 expression was an independent prognostic factor affecting overall survival. in conclusion, the results of this study demonstrated that MYd88 mutation was a valuable index to evaluate the prognosis of dlBcl. ddPcr can be used as a method for detecting MYd88 mutations, although it was not completely consistent with the results of iHc.

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“…Some provocative studies have reported regression of gastric DLBCL after eradication of Helicobacter pylori (found in about 50% of cases), akin to gastric MALT lymphoma [83–85]. In one analysis, 33% of GI lymphomas were non-GCB, whereas MYD88 or CD79B mutations were identified in only <5% [86]. In an examination of 49 cases from Japan, the non-GCB phenotype was seen in 50%, but MYD88 mutation only in 6% [87].…”

Section: Prognosis Of Extranodal Dlbcl Arising From Specific Anatomicmentioning

confidence: 99%

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Ollila

Olszewski

2018

Curr. Treat. Options in Oncol.

112

107

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Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma-risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.

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Mutational frequencies of CD79B and MYD88 vary greatly between primary testicular DLBCL and gastrointestinal DLBCL

Cited by 16 publications

References 15 publications

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma

Prognostic value of MYD88 L265P mutation in diffuse large B cell lymphoma via droplet digital PCR

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

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