Follicular Lymphoma Clinical Trial
Official title:
Constitutional Genetics to Predict Prognostic and Somatic Alterations in Follicular Lymphoma
Follicular lymphoma is the second most common adult B-cell lymphoma. The acquisition of the
t(14;18) translocation is the genetic hallmark of Follicular lymphoma. However, 50% to 70% of
healthy individuals harbor low levels of circulating t(14;18)-positive cells but will never
develop Follicular lymphoma. It was observed that individuals who developed Follicular
lymphoma showed a higher t(14;18) frequency than controls (Roulland et al., J Clin Oncol
2014). High t(14;18) frequency in blood from healthy individuals could be a predictive
biomarker for Follicular lymphoma development. Genetic instability of those t(14;18)+ B-cells
as well as failure of the micro-environment to control the proliferation of these cells are
proposed mechanisms linking these lymphoma precursors to true lymphoma cells. The prognosis
of Follicular lymphoma patients has been significantly improved mainly with the development
of anti-CD20 monoclonal antibodies, with a current median overall survival over 15 years.
However, this lymphoma remains an incurable disease. The most commonly used tool for
prognostication of patients with Follicular lymphoma is the Follicular Lymphoma International
Prognostic Index (FLIPI) based on conventional clinical and pathology parameters. Although it
has clinical utility, the Follicular Lymphoma International Prognostic Index does not reflect
the biologic heterogeneity of Follicular lymphoma. First-degree relatives of Follicular
lymphoma had a fourfold increased risk of Follicular lymphoma suggesting a genetic etiology.
Using the Genome wide association studies (GWAS) approach on Follicular lymphoma cohorts of
1,565 patients, the project plan to identify new prognostic markers. These markers will then
be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology,
using public or matched patient data. The investigators also plan to analyze the influence of
single-nucleotide polymorphisms on circulating t(14;18) levels in 318 healthy individuals
included in EPIC cohort that will develop Follicular lymphoma later on, and assess if these
biomarkers are helpful to refine the identification of high-risk Follicular lymphoma
individuals.
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