Genomic and Proteomic Study of Richter Syndrome (CGPSR)

Study Overview
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Brief Summary
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Biological study on Richter Syndrome (RS), an agressive lymphoma that arises from Chronic Lymphocytice Leukemia (CLL). RS presents with the same histological aspect as primitive Diffuse Large B-Cell Lymphoma (DLBCL), but is associated with a poor prognosis, due to chemorefractoriness. This study aims at understanding the biological determinants of chemotherapy resistance in Richter Syndrome.

Detailed Description
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With the help of the French National Research Group on CLL (FILO / French Innovative Leukemia Organization), the investigators are currently gathering fresh frozen cell pellets at CLL stage, and lymph node biopsies at Richter stage. The investigators also gathered lymph node biopsies from DLBCL, as a reference group. The investigators will perform genomic and proteomic comparative studies between CLL and Richter, as well as between Richter and primitive DLBCL, to understand the biological determinants of clonal evolution and chemorefractoriness of Richter Syndrom.

Official Title
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Genomic and Proteomic Study of Richter Syndrome

Conditions
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Richter Syndrome

Intervention / Treatment
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* Genetic: Whole exome sequencing.
* Genetic: RNA sequencing
* Other: Mass spectrometry


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of a Diffuse Large B-Cell Lymphoma arising in the context of a Chronic Lymphocytic Leukemia (group 1) or diagnosis of a primitive Diffuse Large B-Cell Lymphoma (group 2), or diagnosis of a Diffuse Large B-Cell Lymphoma arising in a context of small cells lymphoma, excluding CLL (group 3), or benefit from a diagnostic lymph node biopsy that did not reveal any tumor involvment (primitive or metastatic) (group 4). Patients must benefit from a lymph node biopsy at diagnosis. Patients must be followed by a FILO (French Innovative Leukemia Organization) member Histology of Diffuse Large B-Cell Lymphoma or Hodgkin histology. Suitable clinical data available. Samples must meet the following requirement :RIN (RNA Integrity Number) > 5 et DIN (DNA Integrity Number) > 6.5. Exclusion Criteria: • Samples that do not meet the inclusion criteria (insufficient clinical data, analysis impossible due to insufficient sample quality).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Richter Syndrom at diagnosis<br>patients diagnosed with Richter Syndrom, for whom a suitable lymph node biopsy at diagnosis is available. | Genetic: Whole exome sequencing.<br>* Retrospective biological exploration of the samples, including tumoral DNA exploration.<br>Genetic: RNA sequencing<br>* Characterization of tumor transcriptomic profile.<br>Other: Mass spectrometry<br>* Characterization of tumor proteomic profiles.<br>|
| Primitive Diffuse Large B-Cell Lymphoma<br>patients diagnosed with a primitive Large B-Cell Lymphoma, for whom a suitable lymph node biopsy at diagnosis is available. | Genetic: Whole exome sequencing.<br>* Retrospective biological exploration of the samples, including tumoral DNA exploration.<br>Genetic: RNA sequencing<br>* Characterization of tumor transcriptomic profile.<br>Other: Mass spectrometry<br>* Characterization of tumor proteomic profiles.<br>|
| Other secundary Diffuse Large B-Cell Lymphoma<br>patients diagnosed with a secundary Large B-Cell Lymphoma (different from Richter Syndrom), for whom a suitable lymph node biopsy at diagnosis is available. | Genetic: Whole exome sequencing.<br>* Retrospective biological exploration of the samples, including tumoral DNA exploration.<br>Genetic: RNA sequencing<br>* Characterization of tumor transcriptomic profile.<br>Other: Mass spectrometry<br>* Characterization of tumor proteomic profiles.<br>|
| Control group with no tumor involvment of lymph nodes<br>patients for whom a diagnostic lymph node biopsy has been performed, which did not conclude to any tumoral lymph node involvment. | Genetic: Whole exome sequencing.<br>* Retrospective biological exploration of the samples, including tumoral DNA exploration.<br>Genetic: RNA sequencing<br>* Characterization of tumor transcriptomic profile.<br>Other: Mass spectrometry<br>* Characterization of tumor proteomic profiles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole exome sequencing data using next generation sequencing method | Comparison between the DNA sequences from Richter syndrome samples and DNA sequences from primitive DLBCL samples to identify a set of mutations that are specific to Richter syndrome. For each position, the result is mutated or unmutated. | 3 years | 
| RNA sequencing data using next generation sequencing method | Measurment of gene expression for all genes. Comparison of these expression levels between Richter samples, primitive DLBCL samples and normal lymph nodes to identifiy a set of genes which expression levels are different in Richter samples compared primitive DLBCL and normal lymph nodes. Gene expression is a quatitative value. This set of genes forms a specific transcriptomic signature of Richter syndrome. | 3 years | 
| Proteomic analysis using mass spectrometry | Mass spectrometry allows identification and measurment of the expression level of the 5,000 most expressed proteins in a sample. The investigators want to compare the protein expression levels between Richter samples, primitive DLBCL samples and normal lymph nodes to identifiy a set of proteins that are highly expressed in Richter samples (but not in primitive DLBCL or normal lymph nodes). This set of proteins forms a specific proteomic signature of Richter. Protein expression is a quatitative value expressed as an absolute number of copies in a cell. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Richter Syndrome, Genomics, Proteomics, Chemotherapy resistance