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.

Public Health Relevance

Since PCNSL is a rapidly fatal disease with an increasing incidence, especially in vulverable populations, this project is relevant to the public health of the nation. In all patients PCNSL has a disproportionate effect on an individual's quality of life because of its disabling impact on cognition, language, mobility, and adaptive skills, but as a primary brain tumor PCNSL also extracts a societal toll estimated at two decades of lost lifetime productivity per person. This goal of this project is to increase the knowledge base of PCNSL to inform effective treatment and prevention strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA137757-02
Application #
7688656
Study Section
Special Emphasis Panel (ZCA1-SRRB-D (O1))
Program Officer
Divi, Rao L
Project Start
2008-09-18
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2011-08-31
Support Year
2
Fiscal Year
2009
Total Cost
$75,550
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905