Thursday, March 13, 2025
3/13/2025
PROJECT SUMMARY GENOMIC BIOMARKERS OF SPLENIC LYMPHOMA Splenic marginal zone lymphoma (SMZL) is the most common form of primary cancer in the spleen. SMZL typically involves the bone marrow and peripheral blood (PB) at presentation. The diagnosis is invariably established in late stages of disease via a splenectomy which is a surgical procedure carrying major risk. Additionally, the diagnosis of SMZL is subjective because there are no specific histopathologic or immunohistochemical biomarkers of the disease. Consequently, early diagnosis of SMZL is challenging and not achieved in most clinical scenarios. Further, SMZLs are among the least reproducibly diagnosed category of lymphomas. The suboptimal diagnostic accuracy necessitates the development of qualitative and objective biomarkers of SMZL. Importantly, while all cases of SMZL are characterized by PB involvement at diagnosis, however this biologic feature has not been leveraged for the reliable early detection of the disease. Using whole genome and exome sequencing, we and others defined the genomic landscape of SMZL and identified recurrently mutated genes in SMZL. An unmet clinical need is the development of reliable biomarkers for the early and accurate diagnosis of the disease based on the characteristic genomic alterations of SMZL. We propose in this application to develop a genomic-based approach that utilizes and validates peripheral blood as for early and accurate diagnosis of the disease. The overall impact of the application is the establishment of a paradigm for early, sensitive and accurate disease diagnosis by analysis of peripheral blood, thereby permitting early and appropriate treatment for the disease.
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