Recurrent Mutations of <i>MYD88</i> and <i>TBL1XR1</i> in Primary Central Nervous System Lymphomas

González-Aguilar, Alberto; Idbaïh, Ahmed; Boisselier, Blandine; Habbita, Naima; Rossetto, Marta; Laurenge, Alice; Bruno, Aurelie; Jouvet, Anne; Polivka, Marc; Adam, Clovis; Figarella‐Branger, Dominique; Miquel, Catherine; Vital, Anne; Ghesquières, Hervé; Gressin, Rémy; Delwail, Vincent; Taillandier, Luc; Chinot, Olivier; Soubeyran, Pierre; Gyan, Emmanuel; Choquet, Sylvain; Houillier, Caroline; Soussain, Carole; Tanguy, Marie Laure; Marie, Yannick; Mokhtari, Karima; Hoang-Xuân, Khê

doi:10.1158/1078-0432.ccr-12-0845

Cited by 222 publications

(187 citation statements)

References 49 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…Future studies in larger cohorts will need to confirm this data in order to update the definition of BNS and to redefine the criteria needed to diagnose BNS. The MYD88 L265P mutation has already been described in nearly one-third of PCNSL cases with an activated B-cell (ABC) diffuse large B cell lymphoma-like profile (Montesinos-Rongen et al, 2011;Gonzalez-Aguilar et al, 2012). High frequency of CD79A/CD79B mutation was also identified in PCNSL.…”

Section: Discussionmentioning

confidence: 92%

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

et al. 2014

View full text Add to dashboard Cite

SummaryBing-Neel syndrome (BNS), a rare neurological syndrome associated with Waldenstr€ om macroglobulinaemia (WM), is a direct involvement of the central nervous system by lymphoplasmacytoid cells characterized with an adverse prognostic. The MYD88 L265P mutation has been identified in the vast majority of patients with WM. The diagnosis of BNS is often challenging because of the variety of clinical presentations associated with difficult histological techniques. We hypothesized that identification of MYD88 L265P mutation in the cerebrospinal fluid (CSF) would contribute to the diagnosis of BNS in addition to imaging, flow cytometry and cytology. We identified MYD88 L265P mutation in the CSF and the bone marrow of all cases of BNS using quantitative polymerase chain reaction qPCR and Sanger sequencing. Copy neutral loss of heterozygosity including MYD88 was observed in one case. No mutation of CXCR4, CD79A and CD79B was observed in parallel. We further showed that monitoring the quantitative expression of MYD88 L265P mutation might be a useful molecular tool to monitor response to chemotherapy using qPCR. In conclusion, identification of MYD88 L265P mutation might be a new molecular-based biomarker tool to add to the diagnostic and monitoring armamentarium for BNS.

show abstract

Section: Discussionmentioning

confidence: 92%

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

et al. 2014

View full text Add to dashboard Cite

show abstract

“…By compiling the results of WES, targeted resequencing (Figure 2A), and high-resolution SNP array analysis ( Figure 2B), 41 genes were recurrently affected in $3 of 35 (9%) of NMZL by mutations (n 5 32 genes) or focal CNA (n 5 9 genes), including MLL2 (also known as KMT2D, 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%) ( Figure 3A; supplemental Tables 3 and 4 . Prevalence of nonsynonymous PTPRD mutations among mature B-cell tumors (NMZL, nodal marginal zone lymphoma, data from this study; SMZL, splenic marginal zone lymphoma, data from this study and others 5,6,7,9 ; DLBCL, diffuse large B-cell lymphoma, data from various studies 22,37,45,47 ; BL, Burkitt lymphoma, data from various studies 40,41 ; CLL, chronic lymphocytic leukemia, data from various studies 38,39,44,49 ; MCL, mantle cell lymphoma, data from Beà et al 43 ; PMBCL, primary mediastinal large B-cell lymphoma, data from Gunawardana et al 15 ; FL, follicular lymphoma, data from various studies 37,48 ; MM, multiple myeloma, data from Chapman et al 36 ; WM, Waldenström macroglobulinemia, data from various studies 42,46 ; EMZL, extranodal marginal zone lymphoma, data from this study; PCNSL primary central nervous system lymphoma, data from various studies [52][53][54][55] ).…”

Section: Recurrent Targets Of Genetic Alterations In Nmzlmentioning

confidence: 84%

The Genetics of Nodal Marginal Zone Lymphoma

Spina

Khiabanian

Messina

et al. 2016

Clinical Lymphoma Myeloma and Leukemia

View full text Add to dashboard Cite

Key Points• PTPRD lesions are among the most recurrent alterations in NMZL and appear to be enriched in this lymphoma type across mature B-cell tumors.• NMZL and SMZL genetics overlap with the exceptions of PTPRD lesions, supporting their distinction as independent entities.Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, wholetranscriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ‡3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%).Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification. (Blood. 2016;128(10):1362-1373

show abstract

“…MYD88 has also been recurrently found mutated at different frequencies in several lymphoid neoplasms, including the majority of Waldenstr€ om macroglobulinemias (90%), in 69% of primary cutaneous leg-type DLBCL, in 38% to 50% of central nervous system lymphomas, in 9% of MALT lymphomas, and in approximately 3% of patients with chronic lymphocytic leukemia (CLL; refs. 11,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. MYD88 L265P mutation is the most frequent and most oncogenic form in DLBCL, although a gain of function triggering an increased production of chemokines has also been demonstrated for other variants (11,34,36).…”

Section: Introductionmentioning

confidence: 99%

MYD88L265P Mutations, But No Other Variants, Identify a Subpopulation of DLBCL Patients of Activated B-cell Origin, Extranodal Involvement, and Poor Outcome

Rovira

Karube

Valera

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Mutations in MYD88 are found in different lymphoproliferative disorders associated with particular biologic characteristics and clinical impact. The aim of this study was to analyze the incidence of MYD88 mutations and its clinical impact in diffuse large B-cell lymphoma (DLBCL).Experimental Design: The incidence, clinicobiological features, and outcome of 213 patients (115 M/98 F; median age, 65 years) with DLBCL treated with immunochemotherapy in a single institution according to MYD88 mutational status as assessed by an allele-specific PCR assay were analyzed. The cell of origin (COO) was determined in 129 cases by gene expression.Results: MYD88 mutations were found in 47 cases (22%), including L265P in 39 and S219C and M232F in 4 cases, respectively. Patients with MYD88 L265P were older, presenting frequent extranodal involvement, and mostly corresponded to activated B-cell like (ABC) subtype, whereas no preference in COO was observed in patients with other MYD88 mutations. Five-year overall survival (OS) for MYD88 wildtype, MYD88 L265P, and other variants was 62%, 52%, and 75%, respectively (P ¼ 0.05). International Prognostic Index (IPI) (HR, 2.71; P < 0.001) and MYD88 L265P (HR, 1.786; P ¼ 0.023) were independent variables predicting OS in the multivariate analysis. However, MYD88 L265P lost its independent value when COO was included in the model.Conclusions: Our findings indicate that MYD88 L265P mutations, but no other variants, identify a subgroup of DLBCL mainly of ABC origin, with extranodal involvement and poor outcome.

show abstract

Recurrent Mutations of MYD88 and TBL1XR1 in Primary Central Nervous System Lymphomas

Cited by 222 publications

References 49 publications

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

The Genetics of Nodal Marginal Zone Lymphoma

MYD88L265P Mutations, But No Other Variants, Identify a Subpopulation of DLBCL Patients of Activated B-cell Origin, Extranodal Involvement, and Poor Outcome

Contact Info

Product

Resources

About