Project: Employing NGS technology for improved, non-invasive early detection, staging and prediction of progression in lymphoma patients

Acronym	NOVEL (Reference Number: transcan-fp-179)
Project Topic	Background, rationale B-cell non-Hodgkin lymphomas (B-NHL) are more frequent in healthy individuals with a family history of lymphoma and in immunocompromised patients. B-NHL display widely heterogeneous clinical behavior: aggressive lymphomas need immediate therapy, though a fraction of cases cannot be effectively treated due to late recognition and/or incorrect staging at diagnosis because of limited sensitivity of the current diagnostic procedures; in contrast, indolent lymphomas do not necessarily need immediate treatment but are bound to long-term repetitive follow-ups (with inevitable psychological and economic burden for many patients who will need none or only late therapies) because of a lack of validated biomarkers able to predict clinical progression requiring treatment. The same uncertainity and burden apply to individuals carrying pre-lymphomatous conditions with inconclusive risk of progression to overt lymphoma.  Hypothesis The gold standard source of material to establish the diagnosis and define the stage (including pre-malignant situations) of most B-NHL is tissue biopsy, an invasive procedure, being physically damaging, painful and even potentially dangerous. This proposal is based on the hypothesis that the use of minimally invasive procedures such as liquid biopsies from peripheral blood assessed by high-throughput analysis of molecular biomarkers will allow to (i) detect early disease through screening populations at risk; (ii) risk-stratify individuals carrying pre-lymphomatous conditions for progression to overt lymphoma; (iii) refine molecular diagnosis and staging in B-NHL.  Aims 1. To detect early disease through screening procedures in populations at risk. 2. To risk-stratify individuals carrying pre-lymphomatous conditions or indolent lymphomas for progression to overt disease. 3. To refine diagnosis and staging in B-NHL.  Methods We will utilize Next Generation Sequencing (NGS) in circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) obtained from peripheral blood samples (a.k.a. liquid biopsy), and perform immunogenetic analysis of the unique IGHV-IGHD-IGHJ monoclonal rearrangements and analysis of recurrently mutated genes in B-NHL/CLL.  Expected results We expect to achieve validated and implemented procedural and analytical pipelines for NGS profiling of B-NHL/CLL-specific biomarkers in liquid biopsies. We will also define validated and implemented bioinformatics workflows and tools for widespread use in a diagnostic setting.  Potential impact The successful completion of the NOVEL proposal will allow to achieve accurate outcome prediction and improved survival through risk stratification of individuals carrying prelymphomatous or indolent conditions for evolution to overt lymphoma and refined molecular diagnosis/staging in the aggressive forms. Potentially, the procedural and analytical pipelines could be utilized also for the management of other neoplastic conditions.
Network	TRANSCAN-2
Call	Third Joint Transnational Call (JTC 2016)

Project partner

Number	Name	Role	Country
1	IRCCS Ospedale San Raffaele	Coordinator	Italy
2	Centre for Research and Technology Hellas (CERTH)	Partner	Greece
3	Erasmus MC	Partner	Netherlands
4	Université Pierre et Marie Curie & Hôpital Pitié-Salpêtrière	Partner	France
5	University Hospital Schleswig-Holstein Campus Kiel	Partner	Germany
6	EXODUS SA	Partner	Greece
7	Utrecht University	Partner	Netherlands