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

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

PROVIDER: PRJNA488476 | ENA |

REPOSITORIES: ENA

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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.

2019-02-19 | GSE119214 | GEO

Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma

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

Sequencing Follicular Lymphoma

Project description:Sequencing Follicular Lymphoma

| PRJNA348784 | ENA

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%).

| EGAS00001006674 | EGA

Follicular Lymphoma expression array

Project description:We used microarrays to detail gene expression profile of several follicular lymphoma patient samples with different grades

2012-04-30 | GSE37088 | GEO

Genomic Analysis of Follicular Lymphoma

Project description:Genomic Analysis of Follicular Lymphoma

| PRJNA856386 | ENA

Genomic Analysis of Follicular Lymphoma

Project description:Genomic Analysis of Follicular Lymphoma

| PRJNA856387 | ENA

Follicular Lymphoma expression array

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

IsomiR Utility in ALS Prognostication [control]

Project description:IsomiR Utility in ALS Prognostication [control]

| PRJNA1321739 | ENA

IsomiR Utility in ALS Prognostication (ALS)

Project description:IsomiR Utility in ALS Prognostication (ALS)

| PRJNA1269625 | ENA