Clinicogenetic Risk Prognostication for First-Line Treatment of Symptomatic Follicular Lymphoma
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PROVIDER: PRJNA488476 | ENA |
REPOSITORIES: ENA
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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.
2019-02-19 | GSE119214 | GEO
Project description:Sequencing Follicular Lymphoma
| PRJNA348784 | ENA
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.
2015-07-16 | GSE66166 | 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.
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
Project description:Genomic Analysis of Follicular Lymphoma
| PRJNA856386 | ENA
Project description:Genomic Analysis of Follicular Lymphoma
| PRJNA856387 | ENA
Project description:We used microarrays to detail gene expression profile of several follicular lymphoma patient samples with different grades
2012-04-30 | GSE37088 | GEO
Project description:Comparison of gene expression profiles of follicular lymphoma vs. reactive lymph nodes. 8 cases of follicular lymphoma; 5 cases of reactive lymph nodes.
2011-09-26 | E-GEOD-14214 | biostudies-arrayexpress
Project description:We used microarrays to detail gene expression profile of several follicular lymphoma patient samples with different grades We analyzed 72 FL samples
2012-04-29 | E-GEOD-37088 | biostudies-arrayexpress