Project description:Nodal marginal zone lymphoma (NMZL) is a rare small B cell lymphoma lacking disease-defining phenotype and precise diagnostic markers. To better understand the mutational landscape of NMZL, particularly in comparison to other small nodal B cell lymphomas, we performed whole exome sequencing, targeted high throughput sequencing and array comparative genomic hybridization on a retrospective series. Our study identified for the first time recurrent, diagnostically useful and potentially therapeutically relevant BRAF mutations in NMZL. Sets of somatic mutations that could help to discriminate NMZL from other closely related small B cell lymphomas were uncovered and tested on unclassifiable small B cell lymphoma cases, in which clinical, morphological and phenotypical features were equivocal. Application of targeted gene panel sequencing gave at many occasions valuable clues for more specific classification.
Project description:This SuperSeries is composed of the following subset Series: GSE32231: Molecular characterization of Nodal marginal zone lymphoma [Gene Expression] GSE32232: microRNA-expression profile in a series of Nodal marginal zone lymphoma patients [miRNA expression] Refer to individual Series
Project description:Primary nodal marginal B cell lymphoma (nMZoL) is rare and is histologically very variable. Its distinction from nodal diffuse large B cell lymphoma (nDLBCL) is often difficult due to the absence of specific markers for marginal zone lymphomas in general. Using a comprehensive cohort of nMZoL and a control cohort of nDLBCL we conducted a methylome analysis on subgroups of both.
Project description:Nodal marginal zone lymphoma is a poorly defined entity in the WHO classification, largely based on criteria by exclusion and the diagnosis often remains subjective. Follicular Lymphoma lacking t(14;18), have similar characteristics which results in a major potential diagnostic overlap which this study aims to dissect. Four subgroups of lymphoma samples (n=56) were analyzed with high-resolution arrayCGH; Nodal marginal zone lymphoma, t(14;18)-negative Follicular Lymphoma, localized t(14:18)-positive Follicular Lymphoma and disseminated t(14;18)-positive Follicular Lymphoma. Gains on chromosomes 7, 8 and 12 were observed in all subgroups. The mean number of aberrations was higher in disseminated t(14;18)-positive Follicular Lymphoma compared to localized t(14:18)-positive Follicular Lymphoma (p<0.01) and the majority of alterations in localized t(14:18)-positive Follicular Lymphoma were also found in disseminated t(14;18)-positive Follicular Lymphoma. Nodal marginal zone lymphoma was marked by 3q gains with amplifications of four genes. A different overall pattern of aberrations was seen in t(14;18)-negative Follicular Lymphoma compared to t(14;18)-positive Follicular Lymphoma. t(14;18)-negative Follicular Lymphoma is marked by specific (focal) gains on chromosome 3 as observed in Nodal marginal zone lymphoma. Our results support the notion that localized t(14:18)-positive Follicular Lymphoma represents an early phase of disseminated t(14;18)-positive Follicular Lymphoma. t(14;18)-negative Follicular Lymphoma bears aberrations that are more alike Nodal marginal zone lymphoma, suggesting a relation between these groups. Four subgroups of follicular lymphoma were analyzed: NMZL (n=14), t-FL (n=12), LOC t+FL (n=16), DIS t+FL (n=14).
Project description:Nodal marginal zone lymphoma is a poorly defined entity in the WHO classification, largely based on criteria by exclusion and the diagnosis often remains subjective. Follicular Lymphoma lacking t(14;18), have similar characteristics which results in a major potential diagnostic overlap which this study aims to dissect. Four subgroups of lymphoma samples (n=56) were analyzed with high-resolution arrayCGH; Nodal marginal zone lymphoma, t(14;18)-negative Follicular Lymphoma, localized t(14:18)-positive Follicular Lymphoma and disseminated t(14;18)-positive Follicular Lymphoma. Gains on chromosomes 7, 8 and 12 were observed in all subgroups. The mean number of aberrations was higher in disseminated t(14;18)-positive Follicular Lymphoma compared to localized t(14:18)-positive Follicular Lymphoma (p<0.01) and the majority of alterations in localized t(14:18)-positive Follicular Lymphoma were also found in disseminated t(14;18)-positive Follicular Lymphoma. Nodal marginal zone lymphoma was marked by 3q gains with amplifications of four genes. A different overall pattern of aberrations was seen in t(14;18)-negative Follicular Lymphoma compared to t(14;18)-positive Follicular Lymphoma. t(14;18)-negative Follicular Lymphoma is marked by specific (focal) gains on chromosome 3 as observed in Nodal marginal zone lymphoma. Our results support the notion that localized t(14:18)-positive Follicular Lymphoma represents an early phase of disseminated t(14;18)-positive Follicular Lymphoma. t(14;18)-negative Follicular Lymphoma bears aberrations that are more alike Nodal marginal zone lymphoma, suggesting a relation between these groups.
Project description:Nodal marginal zone lymphoma (NMZL) is a small B cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile and copy number data from 15 NMZL cases. For comparison, 16 follicular lymphomas, 9 extranodal marginal zone lymphomas, 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by qRT-PCR in an independent series including 61 paraffin-embedded NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NF-kB and TGF-Beta; and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82 and CDC42EP5. Genes linked to G2/M and germinal center were downregulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1, TGFB1 and TACI in NMZL, and BCL6, LMO2 and CD10 in FL. NMZL displayed increased expression of miR-221, miR-223 and let-7f, while FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL.
Project description:Nodal marginal zone lymphoma (NMZL) is a small B cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile and copy number data from 15 NMZL cases. For comparison, 16 follicular lymphomas, 9 extranodal marginal zone lymphomas, 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by qRT-PCR in an independent series including 61 paraffin-embedded NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NF-kB and TGF-Beta; and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82 and CDC42EP5. Genes linked to G2/M and germinal center were downregulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1, TGFB1 and TACI in NMZL, and BCL6, LMO2 and CD10 in FL. NMZL displayed increased expression of miR-221, miR-223 and let-7f, while FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL. We have analyzed gene expression, miRNA profile and copy number data from 15 NMZL cases. For comparison, 16 follicular lymphomas, 9 extranodal marginal zone lymphomas, 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by qRT-PCR in an independent series including 61 paraffin-embedded NMZLs
Project description:Nodal marginal zone lymphoma (NMZL) is a small B cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile and copy number data from 15 NMZL cases. For comparison, 16 follicular lymphomas, 9 extranodal marginal zone lymphomas, 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by qRT-PCR in an independent series including 61 paraffin-embedded NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NF-kB and TGF-Beta; and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82 and CDC42EP5. Genes linked to G2/M and germinal center were downregulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1, TGFB1 and TACI in NMZL, and BCL6, LMO2 and CD10 in FL. NMZL displayed increased expression of miR-221, miR-223 and let-7f, while FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL. Copy number alteration (CNA) was assayed with the DNA from 14 NMZL of frozen-tissue cases, extracted using the standard phenol-chloroform protocol. For CNA, the DNA was hybridized on an Agilent Human Genome CGH Microarray Kit 1 x 44K (Agilent Technologies) following the manufacturer’s instructions. Human female and male pooled gDNA (Promega) was used to normalize the CGH results. Results were considered valuable in 12 cases. The samples (1 μg DNA) were labeled with Cy5 and the DNA donor pool was labeled with Cy3.
Project description:Nodal marginal zone lymphoma (NMZL) is a small B cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile and copy number data from 15 NMZL cases. For comparison, 16 follicular lymphomas, 9 extranodal marginal zone lymphomas, 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by qRT-PCR in an independent series including 61 paraffin-embedded NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NF-kB and TGF-Beta; and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82 and CDC42EP5. Genes linked to G2/M and germinal center were downregulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1, TGFB1 and TACI in NMZL, and BCL6, LMO2 and CD10 in FL. NMZL displayed increased expression of miR-221, miR-223 and let-7f, while FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL.
Project description:Pediatric nodal marginal zone lymphoma (PNMZL) is an unusual and poorly understood primary B-cell nodal neoplasms. Patients are predominantly young males presenting with localized disease. The tumor shows overlapping morphological features with pediatric-type follicular lympgoma. The alterations involved in the pathogenesis of PNMZL are not known.