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Grant Details

Grant Number: 5R03CA137757-02 Interpret this number
Primary Investigator: O'Neill, Brian
Organization: Mayo Clinic Rochester
Project Title: Relationship of 6 (Q)(22) to Survival in Primary Cns Lymphoma
Fiscal Year: 2009
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Abstract

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.

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Publications

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.
Authors: O'Neill B.P. , Decker P.A. , Tieu C. , Cerhan J.R. .
Source: American journal of hematology, 2013 Dec; 88(12), p. 997-1000.
EPub date: 2013-09-12.
PMID: 23873804
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Primary central nervous system lymphomas: a validation study of array-based comparative genomic hybridization in formalin-fixed paraffin-embedded tumor specimens.
Authors: Braggio E. , McPhail E.R. , Macon W. , Lopes M.B. , Schiff D. , Law M. , Fink S. , Sprau D. , Giannini C. , Dogan A. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2011-07-01; 17(13), p. 4245-53.
EPub date: 2011-05-11.
PMID: 21562036
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