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0bc4bd65-a575-4815-9487-37c90ebc4603 - samples

ABSTRACT: We performed targeted NGS in Follicular lymphoma samples at diagnosis. Explored clinico-genetic correlations and assessed four clinical or clinicogenetic risk models (FLIPI, FLIPI-2, PRIMA-IP or m7-FLIPI-molecular score) in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%).

PROVIDER: EGAD00001009647 | EGA |

REPOSITORIES: EGA

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Follicular lymphoma at diagnosis, treated in first line with immunochemotherapy

Project description:We performed targeted NGS in Follicular lymphoma samples at diagnosis. Explored clinico-genetic correlations and assessed four clinical or clinicogenetic risk models (FLIPI, FLIPI-2, PRIMA-IP or m7-FLIPI-molecular score) in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%).

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Clinicogenetic Risk Prognostication for First-Line Treatment of Symptomatic Follicular Lymphoma

Project description:Background: Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with highly variable patient outcomes. Recently, a 23-gene predictor score was proposed for predicting progression-free survival. In the past, we had shown that the m7-FLIPI, a clinico-genetic risk model, allows to improve patient stratification compared to clinical risk models alone. The multitude of prognostic tools in FL raises the question whether they identify common biology. Methods: In this study, we applied a modified risk score (MRS) to an independent gene-expression dataset of FL patients treated with rituximab in combination with chemotherapy. Results: Using supervised and unsupervised approaches, we showed that the MRS identifies patient groups with diverging outcomes in our dataset. In addition, using gene set enrichment and network identification, we discovered associations between the MRS, the m7-FLIPI, EZH2 mutation status and FOXP1 expression. Conclusions: Our findings lend support to expression of dark-zone related genes as a key determinant of poor outcome following rituximab and chemotherapy.

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Project description:Background: Follicular lymphoma (FL) is a clinically and genetically heterogeneous disease. The prognostic value of somatic mutations has not been systematically evaluated and no genetic factors have been identified that distinguish patients at highest risk of treatment failure. Methods: We performed deep sequencing of 74 genes in 151 patients treated with R-CHOP from a phase III trial. Mutations and clinical factors were incorporated into a risk model using multivariable L1-penalized Cox regression. We validated the risk model in an independent cohort of 107 patients treated with R-CVP. Results: The final clinicogenetic index, the “m7-FLIPI”, contained the FL International Prognostic Index (FLIPI), ECOG performance status, and mutation status of 7 genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP and CARD11). In the training cohort, the m7-FLIPI defined a high-risk group (28% of patients) with 5-year failure-free survival (FFS) of 38% vs 77% for the low-risk group (Hazard ratio (HR) 4.1, confidence Interval (CI)=[2.5;6.9], p<0.0001). In the validation cohort, the m7-FLIPI defined a high-risk group (22% of patients) with 5-year FFS of 25% versus 68% (HR 3.6, CI=[2.0;6.4], p<0.0001) in the low-risk group. In both cohorts, the m7-FLIPI outperformed the FLIPI alone. Strikingly, all 66 patients with EZH2 mutations in both cohorts were categorized as low-risk m7-FLIPI, and EZH2 mutations defined a distinct transcriptional profile. Conclusions: The combination of clinical factors and mutations in 7 genes can identify the subset of patients with FL at highest risk of treatment failure. The m7-FLIPI can be widely utilized for risk prognostication and patient stratification.

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Developmental stage-specific interplay between GATA1 and IGF signaling in fetal hematopoiesis and leukemogenesis

Project description:This SuperSeries is composed of the following subset Series: GSE16676: Rescue of murine Gata1s mutant M7 leukemic cells by full-length Gata1 GSE16677: Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples GSE16679: Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia GSE16682: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors GSE16684: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors depends on IGF signaling Refer to individual Series

2010-08-01 | E-GEOD-16655 | biostudies-arrayexpress

Differences Between Follicular Lymphoma With and Without Translocation t(14;18)

Project description:Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFƒÛB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.

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The RPB2 flap loop of human RNA polymerase II is dispensable for transcription initiation and elongation.

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Streptomyces sp. M7 LC-MS - Streptomyces sp. M7 has demonstrated ability to remove lindane from culture media and soils

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