||5R03CA137757-02 Interpret this number
||Mayo Clinic Rochester
||Relationship of 6 (Q)(22) to Survival in Primary Cns Lymphoma
DESCRIPTION (provided by applicant):
ABSTRACT PCNSL (primary central nervous system lymphoma) is an aggressive primary brain tumor characterized by the perivascular accumulation of malignant cells that have lymphoid characteristics. It is currently accepted as a unique extranodal non-Hodgkin's lymphoma (NHL). The molecular pathogenesis of PCNSL is not known. PTPRK protein, a regulator of growth factor receptor-mediated phosphorylation that maps to gene locus 6q22-23, may act as a tumor suppressor in PCNSL. Two recent projects by our group suggested that 1. In one Mayo-based project deletion of 6q22-23/PTPRK correlated with shorter patient survival seemingly independent of other cytogenetic abnormalities, treatment time trends, or patient age. 2. In a second SEER Registry-based project Black Americans and White Americans appeared to have significantly differing incidence and survival rates suggesting a genetic factor. We propose to confirm these observations in a population-based setting by interrogating PCNSL specimens from the Iowa, LA County and Hawaii SEER Discard Repositories. We will interrogate these tissues to determine the frequency of deletion of 6q22-23, and in particular deletion of the tumor suppressor gene PTPRK; to determine the association between PTPRK deletions and PTPRK protein expression; and, lastly, to correlate these data with the richly annotated SEER data that includes incidence and survival. The primary focus of this application is etiologic cancer research. Our preliminary data suggests a basis for more extended research. The R03 mechanism was selected to validate observations made in clinical specimens from an NCI-supported resource as a prelude to more detailed investigation. This is a first step in an investigative cascade that will explore racial and genetic influences on PCNSL tumorigenesis.
The changing incidence of primary central nervous system lymphoma is driven primarily by the changing incidence in young and middle-aged men and differs from time trends in systemic diffuse large B-cell non-Hodgkin's lymphoma.
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