Targeted Mutational Analysis of Enteropathy-Associated T-cell Lymphoma
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ABSTRACT:
PROVIDER: PRJNA322362 | ENA |
REPOSITORIES: ENA
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Project description:Type II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Here we performed gene expression profiling on four Type II EATL samples in order to better characterize this disease. As Type II EATL is suggested to arise from CD8+ IELs, we integrated our data with publicly available profile of CD8αα and CD8αβ T-cells from healthy donors (GSE33374). Gene expression profiling independently demonstrated strong enrichment of several aspects of GPCR and JAK-STAT signaling pathways. Moreover, an significant association was identified with genes containing STAT5B binding sites in their promoters. Microarray gene expression profiling was performed on 4 Type II Enteropathy-associated T-cell lymphoma and a combination of unsupervised and supervised clustering was performed to determine any differentially activated pathways between samples with tumor and healthy human CD161++CD8aa and CD161++CD8ab T cells (found under accession number GSE33374)
2016-03-03 | E-GEOD-70652 | biostudies-arrayexpress
Project description:Type II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Genome-wide DNA copy number profiling of Type II EATL tumors and matched normal samples was performed to determine copy-number changes in this disease.
2016-03-03 | GSE70653 | GEO
Project description:Type II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Genome-wide DNA copy number profiling of Type II EATL tumors and matched normal samples was performed to determine copy-number changes in this disease. Affymetrix SNP6 arrays were performed according to the manufacturer's directions on gDNA extracted from 4 tumors and 4 matched whole blood samples.
2016-03-03 | E-GEOD-70653 | biostudies-arrayexpress
Project description:Type II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Here we performed gene expression profiling on four Type II EATL samples in order to better characterize this disease. As Type II EATL is suggested to arise from CD8+ IELs, we integrated our data with publicly available profile of CD8αα and CD8αβ T-cells from healthy donors (GSE33374). Gene expression profiling independently demonstrated strong enrichment of several aspects of GPCR and JAK-STAT signaling pathways. Moreover, an significant association was identified with genes containing STAT5B binding sites in their promoters.
2016-03-03 | GSE70652 | GEO
Project description:Approximately 2–5% of adult-onset coeliac disease (CD) patients develops refractory coeliac disease (RCD). In contrast to RCD type I, RCD type II is characterised by the presence of aberrant small intestinal intraepithelial T-lymphocytes (IEL) expressing cytoplasmic CD3 but lacking surface expression of CD3, CD4 and CD8. Development of Enteropathy Associated T-cell Lymphoma (EATL) is directly associated with the presence of >20% aberrant IEL in RCD II patients and has a very poor prognosis. We report on an exceptional case of EATL presenting as leukemic ascites and on the unique opportunity to perform extensive phenotypic and genomic analysis of this malignancy. Flow cytometric immunophenotyping of the ascitic EATL presentation showed CD30 expression typical for EATL and loss of the above mentioned surface markers similar to the aberrant IEL it originated from, as indicated by an identical monoclonal TCR-gamma rearrangement. In addition, expression of a substantial number of markers, including CD2, CD7, CD11a/CD18, CD52, CD103 and granzyme B was lost, which has not been reported sofar. Expression of proliferation markers Ki-67 en PCNA was clearly detected in the majority of EATL cells. Karyotype and comparative genomic hybridisation (CGH) analyses showed many genomic alterations, including chromosomal gains and losses up to 47Mb not previously reported for EATL. In conclusion, the current exceptional EATL presentation displays both immunophenotypic and genomic alterations not described previously and not included in the current WHO classifications of lymphoid malignancies. Comparative genomic hybridisation (CGH) analyses of an exceptional case of enteropathy associated T cell lymphoma
2010-06-17 | E-GEOD-17715 | biostudies-arrayexpress
Project description:Targeted Mutational Analysis of Enteropathy-Associated T-cell Lymphoma
| PRJNA322363 | ENA
Project description:Approximately 2–5% of adult-onset coeliac disease (CD) patients develops refractory coeliac disease (RCD). In contrast to RCD type I, RCD type II is characterised by the presence of aberrant small intestinal intraepithelial T-lymphocytes (IEL) expressing cytoplasmic CD3 but lacking surface expression of CD3, CD4 and CD8. Development of Enteropathy Associated T-cell Lymphoma (EATL) is directly associated with the presence of >20% aberrant IEL in RCD II patients and has a very poor prognosis. We report on an exceptional case of EATL presenting as leukemic ascites and on the unique opportunity to perform extensive phenotypic and genomic analysis of this malignancy. Flow cytometric immunophenotyping of the ascitic EATL presentation showed CD30 expression typical for EATL and loss of the above mentioned surface markers similar to the aberrant IEL it originated from, as indicated by an identical monoclonal TCR-gamma rearrangement. In addition, expression of a substantial number of markers, including CD2, CD7, CD11a/CD18, CD52, CD103 and granzyme B was lost, which has not been reported sofar. Expression of proliferation markers Ki-67 en PCNA was clearly detected in the majority of EATL cells. Karyotype and comparative genomic hybridisation (CGH) analyses showed many genomic alterations, including chromosomal gains and losses up to 47Mb not previously reported for EATL. In conclusion, the current exceptional EATL presentation displays both immunophenotypic and genomic alterations not described previously and not included in the current WHO classifications of lymphoid malignancies.
2010-06-17 | GSE17715 | GEO
Project description:Expression and Mutational Analysis of Endemic Burkitt Lymphoma
| PRJNA369584 | ENA
Project description:Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Although targeted sequencing studies and a single center whole exome sequencing (WES) study in HIV+ patients recently revealed several genes, associated with PBL pathogenesis, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns and perturbed pathways in HIV+ and HIV- PBL we performed WES and RNA-sequencing (RNA-seq) of 34 PBL tumors.
| EGAS00001004906 | EGA
Project description:Enteropathy-associated T cell lymphoma (EATL) is a lethal and the most common neoplastic complication of celiac disease. In this study, we applied whole exome sequencing in 69 EATL tumors to define the genetic landscape of EATLs. The most frequently mutated gene in EATL was SETD2 (32% of cases), with loss of function mutations comprising a large proportion (41%) of those mutations. The JAK-STAT pathway was the most frequently mutated signaling pathway, with mutations in STAT5B being the most common, followed by JAK1, JAK3, STAT3, and the negative regulator of the pathway, SOCS1. We also identified mutations in NRAS and KRAS, as well as TP53 and TERT. Interestingly, the two types of EATL had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. Gene expression analysis of the two types of EATL identify robust differences in transcriptional profiles. We further modeled the effects of SETD2 loss in vivo by developing a T cell specific knockout mouse model. These mice manifested an expansion of γδ T cells that identify novel roles for SETD2 in T cell development and lymphomagenesis. Together, our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease, and may inform future classification schemes.
| EGAS00001001954 | EGA