The incidence of non-Hodgkin's lymphoma (NHL) has been rising more rapidly than that of most other cancers, and accounts for approximately 53,000 new cases of cancer annually. The most dramatic increases have been in the category of diffuse large cell lymphomas, which are aggressive neoplasms with short median survival. Diffuse large B-cell lymphoma (DLBCL) may arise de novo, or as the end result of histologic progression from a pre-existing low grade B-cell lymphoma. Accumulating experimental evidence suggests that secondary genetic alterations such as p53 gene mutations or inactivation of the p16INK4A gene in low-grade follicular lymphomas (LGFCL) are associated with histologic transformation to DLBCL. Prior studies have only examined one or a few possible genes that may be implicated in lymphoma progression. It is the investigators hypothesis that multiple molecular aberrations may accompany histologic transformation from LGFCL into DLBCL. They propose to employ microarray analysis in the determination of the important molecular changes associated with histologic progression, by studying matched pairs of LGFCL and DLBCL occurring in the same patient. They shall verify clonal identity in the two tumors by immunoglobulin heavy chain gene PCR analysis, and establish the presence of the characteristic t(14;18) translocation in both samples in order to ensure that both neoplasms originate from a follicular lymphoma. The microarray technology permits the simultaneous study of the expression status of multiple genes and will provide insights into the common patterns of gene dysregulation that contribute to lymphoma progression. Elucidation of these molecular aberrations will allow the delineation of distinct progressed lymphoma subgroups, the identification of molecular prognostic factors, and the development of novel therapeutic targets that are directed at the specific molecular aberrations.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA083984-02
Application #
6342195
Study Section
Pathology B Study Section (PTHB)
Program Officer
Thurin, Magdalena
Project Start
2000-01-14
Project End
2002-12-31
Budget Start
2001-01-19
Budget End
2002-12-31
Support Year
2
Fiscal Year
2001
Total Cost
$112,519
Indirect Cost
Name
University of Utah
Department
Pathology
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Elenitoba-Johnson, Kojo S J; Bohling, Sandra D; Jenson, Stephen D et al. (2002) Fluorescence PCR quantification of cyclin D1 expression. J Mol Diagn 4:90-6
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