Overlap Between Pediatric Nodal Marginal Zone Lymphoma (PNMZL) and Pediatric-Type Follicular Lymphoma (PTFL) : Morphological and Molecular Analysis (CytoScan)
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PROVIDER: PRJNA746081 | ENA |
REPOSITORIES: ENA
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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.
2022-07-11 | GSE154830 | GEO
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.
2022-07-11 | GSE154831 | GEO
Project description:Overlap Between Pediatric Nodal Marginal Zone Lymphoma (PNMZL) and Pediatric-Type Follicular Lymphoma (PTFL) : Morphological and Molecular Analysis
| PRJNA647789 | ENA
Project description:Overlap Between Pediatric Nodal Marginal Zone Lymphoma (PNMZL) and Pediatric-Type Follicular Lymphoma (PTFL) : Morphological and Molecular Analysis (OncoScan)
| PRJNA746078 | ENA
Project description:Nodal marginal zone lymphoma (NMZL) is one of the few B-cell tumors still remaining orphan of cancer gene lesions. By combining whole exome sequencing (WES), deep sequencing of tumor-related genes, high resolution SNP array and RNAseq, here we aim at characterizing the coding genome of NMZL and at disclosing the pathways that are molecularly deregulated in this lymphoma. The study was based on 35 NMZL (tumor representation >70%) with a diagnosis confirmed by: i) pathological revision of lymph node histology; and ii) lack of clinico-radiological evidence of extranodal or splenic disease either at diagnosis or during follow-up. Consistent with NMZL, the cases investigated: i) lacked CD5, CD10 and cyclin D1 expression, 7q deletion, t(11;14), t(14;18), t(11;18) and t(1;14) translocations; and ii) recurrently harbored +3 (14%), +12 (14%) and preferential usage of the IGHV4-34 gene (17%). WES (HiSeq 2500, Illumina; mean coverage per sample: 38x-114x) and high resolution SNP array (Cytoscan HD, Affymetrix) of tumor/normal DNA pairs from 18 discovery NMZL identified 557 non-synonymous somatic mutations (average: 30.8/case) affecting 504 genes and 51 copy number abnormalities (CNA) (average: 3.2/case). To further characterize mutation recurrence, the 504 discovered genes were investigated in an independent validation panel of 17 NMZL by targeted sequencing of tumor/normal DNA pairs (MiSeq; target region: 1.6 Mb; mean coverage per sample: 171x-386x). The 17 validation NMZL were also assessed for CNA by high resolution SNP arrays. RNAseq of 11 discovery NMZL did not identify any recurrent gene fusion. By compiling the results of WES and high resolution SNP array, 39 genes were recurrently affected in >3/35 (9%) NMZL by mutations (n=30 genes) or focal CNA (n=9 genes). Among these, MLL2 (34%), PTPRD (20%) and NOTCH2 (20%) were most frequently mutated. Overall, recurrently mutated genes pointed to the molecular deregulation of specific programs in NMZL, namely JAK/STAT, NOTCH, NF-κB and toll-like receptor (TLR) signaling, cell cycle, chromatin remodeling/transcriptional regulation and immune escape (Fig. 1A). JAK/STAT signaling was targeted by mutually exclusive lesions in 43% of NMZL, and the protein tyrosine phosphatase receptor delta (PTPRD) tumor suppressor was the most frequently affected gene of this system in 20% of NMZL (Fig. 1B-E). PTPRD inhibits JAK/STAT signaling through the dephosphorylation of active p-STAT3. PTPRD lesions in NMZL were represented by somatic mutations that truncated or modified the tyrosine phosphatase domain, as well as deletions of the entire gene locus, including focal and biallelic losses (Fig. 1B-C). Interrogation of institutional and public genomic datasets revealed that PTPRD mutations are specific for NMZL, being rare or absent in other mature B-cell tumors, including splenic marginal zone lymphoma (Fig. 1D). Other JAK/STAT signaling genes affected in NMZL were JAK2, CXCR4 (6%), PTPN2, JAK3, STAT2, SH2B3 and CUL3 (3%) (Fig. 1E). NF-kB signaling was altered in 54% of NMZL by lesions of TNFAIP3 (14%), BCL10, REL (11%), CARD11 (9%), TRAF3 and BIRC3 (6%). NOTCH signaling was targeted in 40% of NMZL by mutations that alternatively involved NOTCH2 (20%), SPEN (11%), RBPJL (6%), FBXW7, DTX1, ITCH and MAML2 (3%). TLR signaling was targeted in 17% of NMZL, including mutations of MYD88 (9%), IRAK1BP1, PELI2 and SEMP6 (3%). Several cell cycle genes were molecularly deregulated in 43% of NMZL, including CDKN2A, PARK2, PARKG (9%), CDC16, CDCA2 (6%), CCNA1, CCNT2, CDK5, CDK13, CDK20, BTG2, HECA and PLK2 (3%). Most (71%) NMZL harbored genetic lesions affecting epigenetic modifiers (MLL2: 34%; CREBBP: 9%; EP300: 6%; TRRAP: 6%), histones (20%) or transcriptional co-repressors (TBL1XR1: 14%; ARID1A: 14%; RCOR1: 11%; NCOR2: 9%, ARID1B: 9%). Finally, the TNFRSF14 and FAS genes, involved in T cell-mediated tumor surveillance, were disrupted by mutations and/or deletions in 17% and 14% NMZL, respectively. A number of actionable cellular programs are molecularly deregulated in NMZL, including JAK/STAT, NOTCH, NF-κB and TLR signaling, cell cycle and chromatin remodeling. PTPRD lesions are among the most recurrent alterations in NMZL and appear to be specific for this lymphoma type across mature B-cell tumors. Cytoscan HD arrays (Affymetrix, Santa Clara, CA) experiments were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic samples.
2015-12-01 | GSE68078 | GEO
Project description:Global genetic profiling of a pediatric series of T-cell lymphoblastic lymphoma [Cytoscan]
| PRJNA738942 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-07-11 | GSE154834 | GEO
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
2011-09-20 | E-GEOD-32233 | biostudies-arrayexpress
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.
2013-07-16 | GSE40641 | GEO
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).
2013-07-16 | E-GEOD-40641 | biostudies-arrayexpress