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Chromosomal Translocations in Non-Hodgkin Lymphoma in the PLCO Etiology Cohort Study

Principal Investigator
Name
Charles Rabkin
Degrees
-
Institution
NCI, DCEG, IIB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2006-0302
Initial CDAS Request Approval
Dec 29, 2006
Title
Chromosomal Translocations in Non-Hodgkin Lymphoma in the PLCO Etiology Cohort Study
Summary
Chromosomal translocations (CTs) that result in the deregulated expression of oncogenes or the generation of novel fusion genes are hallmark mutations of hematopoietic malignancy. An important example is the t(14;18)(q32;q21) which leads to constitutive activation of the BCL2 oncogene. This CT is typically present in tumor cells of follicular lymphoma as well as a fraction of other non-Hodgkin lymphomas (NHL). However, CT may not be a sufficient cause of malignant transformation, since a low frequency of t(14;18) is also detectable in peripheral blood mononuclear cells (PBMC) from up to 50% of healthy individuals. We propose to investigate whether the prevalence or frequency of t(14;18) is associated with risk of subsequent NHL in the PLCO Etiology Study cohort. Access to tumor tissue would enable comparison of translocation sequence in the lymphoma to that in pre-diagnostic peripheral blood. These studies will elucidate whether the CT-bearing cells are clonally related and hence the relative timing of this mutation in lymphomagenesis. A better understanding of the special biology of t(14;18)-positive cells in healthy individuals could provide insight into their potential role as tumor precursors that may, in some instances, become clonogenic founders of NHL.
Aims

1) To determine whether prevalence and/or frequency of PBMC t(14;18) is associated with risk of subsequent NHL, and examine correlates and predictors of these abnormalities. 2) To determine the clonal relationship and evolution of pre-diagnosis t(14;18)-bearing PBMC to subsequent NHL tumors

Collaborators

Richard Hayes (NCI, DCEG)
Casrten Hirt (U. Greifwald (Germany) Heme/Onc)
Siegfried Janz (NCI CCR)
Ruth Pfeiffer (NCI, DCEG)
Charles Rabkin (NCI, Viral Epidemiology Branch)
Kelly Yu (NCI, DCEG)

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