Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation

Martínez, Nerea; Almaráz, Carmen; Vaqué, José P.; Varela, Ignacio; Derdak, Sophia; Beltrán, Sergi; Mollejo, Manuela; Campos-Martín, Yolanda; Águeda, Lídia; Rinaldi, Andrea; Kwee, Ivo; Gut, Marta; Blanc, Julie; Oscier, David; Strefford, Jonathan C.; Martínez‐López, Joaquín; Salar, Antonio; Solé, Françesc; Rodríguez-Peralto, José L.; Diez-Tascón, Cristina; Garcı́a, Juan F.; Fraga, Máximo; Sebastián, Elena; Alvés, Javier; Menárguez, Javier; González-Carreró, Joaquín; Casado, L.F.; Bayés, Mònica; Bertoni, Francesco; Gut, Ivo; Piris, Miguel Á.

doi:10.1038/leu.2013.365

Cited by 98 publications

(66 citation statements)

References 49 publications

(51 reference statements)

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“…In particular, NOTCH2, known as a key regulator of MZ development, was the most frequently mutated gene (20%) This frequency is consistent with the prevalence of NOTCH2 mutations documented in SMZL 5,6,18,25,26 and significantly higher than that observed in HCV-negative DLBCL (this study), and more in general, in unselected DLBCL cohorts 27,28 (Online Supplementary Table S4). All NOTCH2 mutations observed in HCV-positive DLBCL cause disruption of the protein inhibitory PEST domain and are predicted to activate NOTCH signaling.…”

Section: Discussionsupporting

confidence: 73%

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

et al. 2014

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Section: Discussionsupporting

confidence: 73%

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

et al. 2014

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“…3). BIRC3 inactivating mutations have been described in CLL, SMZL [91] and MCL [92,93], while TRAF3 mutations can be observed in CLL [4,10,11], SMZL [48, 94,95], DLBCL [96] and myeloma [97,98].…”

Section: Implication Of the Bcr Tlr Pathwaysmentioning

confidence: 99%

Chronic lymphocytic leukemia: Time to go past genomics?

2016

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Recent advances in massively parallel sequencing technologies have provided a detailed picture of the mutational landscape in CLL and underscored the vast degree of interpatient and intratumor heterogeneities. These studies have led to the characterization of novel putative driver genes and recurrently affected biological pathways, and to the modeling of CLL clonal evolution. We herein review selected aspects including recent advances in the biology of CLL and present cellular and biological processes involved in the development of CLL and potentially other mature B-cell lymphoproliferative neoplasms.

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“…If CBL-MZ are to be considered the early stage of SMZL, they should share a common genetic profile with this lymphoma, including recurrent NOTCH2 mutations and, more generally, mutually exclusive lesions affecting signalling pathways involved in normal MZ differentiation (Kiel et al, 2012;Rossi et al, 2012;Parry et al, 2013;Mart ınez et al, 2014). Otherwise, if CBL-MZ represent the early phase of a SLLU, they might harbour MAP2K1 mutations and lack lesions of MZ differentiation genes (Waterfall et al, 2014).…”

Section: Molecular Lesions Of Signalling Pathway Genes In Clonal B-cementioning

confidence: 99%

Molecular lesions of signalling pathway genes in clonal B‐cell lymphocytosis with marginal zone features

et al. 2014

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Molecular lesions of signalling pathway genes in clonal B-cell lymphocytosis with marginal zone featuresClonal B-cell expansions whose immunophenotype is consistent with marginal zone (MZ) lymphoma, but presenting with isolated lymphocytosis in the absence of splenomegaly or lymph node enlargements, cannot be assigned to any of the entities recognized by the World Health Organization (WHO) classification of haematological malignancies (Swerdlow et al, 2008). After reviewing the clinico-pathological features of such cases, Xochelli et al (2014) proposed that these lymphoproliferations: (i) may represent the early stage of a splenic marginal zone lymphoma (SMZL) or of a splenic B-cell lymphoma/leukaemia unclassifiable (SLLU); and (ii) should be classified as a provisional entity, termed clonal B-cell lymphocytosis with marginal zone features (CBL-MZ) in future classifications of mature B-cell tumours.Along with clinico-pathological features, the WHO classification also utilizes genetic data to define distinct and provisional entities (Swerdlow et al, 2008). If CBL-MZ are to be considered the early stage of SMZL, they should share a common genetic profile with this lymphoma, including recurrent NOTCH2 mutations and, more generally, mutually exclusive lesions affecting signalling pathways involved in normal MZ differentiation (Kiel et al, 2012;Rossi et al, 2012;Parry et al, 2013;Mart ınez et al, 2014). Otherwise, if CBL-MZ represent the early phase of a SLLU, they might harbour MAP2K1 mutations and lack lesions of MZ differentiation genes (Waterfall et al, 2014).To unravel the genetics of CBL-MZ, mutations of the NOTCH2, NOTCH1, BIRC3, TNFAIP3, TRAF3, IKBKB, MYD88, CD79A, CD79B, CARD11, BRAF and MAP2K1 genes were investigated on peripheral blood (PB) samples (tumour representation >50%) from 16 CBL-MZ identified according to the criteria defined by Xochelli et al (2014), namely: (i) persistent monoclonal B-cell lymphocytosis in the PB; (ii) immnophenotypic features consistent with a MZ lymphoproliferation, including lack of CD5, CD10, and CD103 expression and a Matutes score <2; (iii) bone marrow (BM) infiltration by small lymphocytes with no or limited plasmacytic differentiation; (iv) absence of lymphadenopathy, splenomegaly or extranodal tissue organomegaly by computerized tomography scan. BM biopsies were reviewed by experienced haematopathologists. Patients provided informed consent in accordance with the Declaration of Helsinki. The study was approved by the Ethical Committee (Protocol Code CE 116/12).Median absolute lymphocyte count of CBL-MZ was 11Á4 9 10 9 /l (range: 4Á5-23Á9 9 10 9 /l) and the median tumour B-cell count was 8Á1 9 10 9 /l (range: 3Á4-19Á8 9 10 9 /l) ( Table SI). According to current diagnostic criteria, 43% (7/16) could be classified as non-CLL type of monoclonal B-cell lymphocytosis (Marti et al, 2005). A small (<10 g/l) serum monoclonal component of IgM type was detected in 25% of cases (95% confidence interval [CI]: 9-49%; n = 4/16). After a median follow-up of 44 months, 18% (95% CI: 5-...

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Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation

Cited by 98 publications

References 49 publications

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

Chronic lymphocytic leukemia: Time to go past genomics?

Molecular lesions of signalling pathway genes in clonal B‐cell lymphocytosis with marginal zone features

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