Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Lymphoma, Follicular

Genetic Predisposition to Disease

Disease Susceptibility

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Disease Attributes

Lymphosarcoma

Follicular Lymphoma

Patients are adults, male or female, with a follicular lymphoma, homogeneously treated by immunochemotherapy included in one of the following cohorte :

* PRIMA Cohort : phase III (Sponsor LYSARC, France; NCT00140582): N=396
* RELEVANCE Cohort : phase III (Sponsor LYSARC, France; NCT01476787 ): N=441
* FOLL05 Cohort: phase III (Sponsor Italian lymphoma Foundation, Italy; NCT00774826): N=229
* MER1 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987): N=178
* MER2 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987):N=321

Using the Genome wide association studies (GWAS) approach on these 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.

Patients are adults, male or female, included in the EPIC Cohort (European Prospective Investigation Into Cancer and Nutrition study between 1992 and 2000. (Sponsor IARC, Lyon, France).

The investigators plan to analyze the influence of single-nucleotide polymorphisms on circulating t(14;18) levels in these 318 healthy individuals including 100 who will develop follicular lymphoma later on, and assess if these biomarkers are helpful to refine the identification of high-risk follicular lymphoma individuals.

Using the Genome wide association studies (GWAS) approach on these 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.

Genome Wide Association Studies

Analyze of the influence of single-nucleotide polymorphisms on circulating t(14;18) levels

Single-nucleotide polymorphisms's genotyping

Hervé Ghesquières, Pr

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.

Constitutional Genetics in Follicular Lymphoma

Constitutional Genetics to Predict Prognostic and Somatic Alterations in Follicular Lymphoma

Event Free Survival for follicular lymphoma patients treated with modern immunochemotherapy in five cohorts is the primary end point defined as the time from the diagnosis or randomization to the date of progression, relapse, re-treatment, or death from any cause.

Two steps analysis, with a discovery cohort and a validation cohort :

The discovery cohorts that the investigators plan to study are a subset of patients with available deoxyribonucleic acid samples of two prospective phase III trials (PRIMA (NCT00140582) (N=396) and FOLL-05 (NCT00774826) (N=229), and one prospective observational cohort SPORE of the University of Iowa-Mayo Clinic (MER1; N=178). A GWAS will then be performed on a subset of patients with available deoxyribonucleic acid of two validation cohorts (Prospective observational SPORE MER2; N=321, phase III trial RELEVANCE, NCT01476787, N=441).

In order to better decipher the impact of host genetics on somatic alterations and tumor biology and understand the physiological function of the single-nucleotide polymorphism identified from the primary outcome measure, we will study the link between the molecular profiles of the tumor and the prognostic single-nucleotide polymorphism. This will be performed on samples of the PRIMA and MER studies, for which we have access to somatic and constitutive data.

In parallel, we will investigate the relation between known susceptibility single-nucleotide polymorphism and the level of the t(14 ;18) translocation. The latter analysis will be performed on EPIC samples (European Prospective Investigation Into Cancer and Nutrition), comparing healthy individuals to individuals who developed a follicular lymphoma. Finally, we will assess the effect of susceptibility single-nucleotide polymorphism on somatic molecular profiles on PRIMA and MAYO cohorts.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Constitutional Genetics in Follicular Lymphoma	NCT03234140	Follicular Lymp... Genetic Predisp...	Genome Wide Ass... Single-nucleoti...	18 Years -	Hospices Civils de Lyon
Constitutional Genetics in Follicular Lymphoma	NCT03234140	Follicular Lymp... Genetic Predisp...	Genome Wide Ass... Single-nucleoti...	18 Years -	Hospices Civils de Lyon
Constitutional Genetics in Follicular Lymphoma	NCT03234140	Follicular Lymp... Genetic Predisp...	Genome Wide Ass... Single-nucleoti...	18 Years -	Hospices Civils de Lyon

Spots Global Cancer Trial Database for genome wide association studies