Quantitative proteomic analysis of lymphoma transformation

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DESCRIPTION (provided by applicant): Non-Hodgkin's lymphoma accounts for approximately 50,000 new cases of cancer annually. This figure represents an increase beyond that seen for most other forms of cancer. Among the non-Hodgkin's lymphomas, follicular lymphoma represents the most common subtype of low-grade B-cell lymphoma in adults, and typically pursues an indolent clinical course. In a significant proportion of cases there is histologic transformation from a low-grade neoplasm to an aggressive diffuse large B-cell lymphoma with significantly decreased median survival. The recent advent of sophisticated mass spectrometry technology coupled with software algorithms that permit instantaneous protein identification, makes it feasible to study the pattern of protein deregulation that distinguish two biologic states. We propose to employ a combination of chromatographic techniques and tandem mass spectrometry in the identification of the alterations in protein expression that accompany histologic transformation. We shall be analyzing a cohort of matched pairs of follicular lymphoma and their transformed diffuse large B-cell lymphoma counterparts occurring in the same individual. Relevance: Comprehensive identification of the qualitative and quantitative changes in protein expression that are involved in follicular lymphoma transformation will permit the delineation of deregulated pathways, identify distinct prognostic subgroups of transformed lymphoma, and facilitate the development of novel therapies that target susceptible elements in the deregulated pathways.