Non-Hodgkin's lymphomas (NHLs) are the 5th most common malignancy in the United States, with an incidence that has increased significantly over the last decade. Preliminary data obtained from Adult Lymphoma clinic at DFCI, as well as from Hodgkin's lymphoma patients treated at the Harvard Joint Center for Radiation Therapy (JCRT), show that 6-9% of these patients have a first-degree relative who also has a lymphoproliferative disorder. The goals of this research proposal are to systematically identify and characterize the subset of lymphomas associated with apparent familial predisposition and to determine whether their genetic basis can be identified.
The Specific Aims of this project are: (1) to identify families with at least two first-degree relatives with lymphoproliferative malignancy and establish a data and tissue bank including serum, peripheral blood lymphocytes, germline DMA, and tumor tissue; (2) to investigate whether familial lymphomas have characteristic sites of loss of heterozygosity and to attempt to identify candidate genes within those regions; (3) to investigate whether familial lymphomas have characteristic patterns of global gene expression; (4) to perform a linkage analysis to identify candidate genes in the germline that may predispose to lymphoma development. These novel experiments should illuminate the biological underpinnings of familial lymphoma, which should in turn lead to targeted therapies and possibly methods of screening or prevention. This project will enable the candidate to use her scientific training in molecular biology to develop an academic career in clinical / translational investigation in lymphoma, applying novel scientific discoveries to the clinic. The research will be conducted primarily at Dana-Farber Cancer Institute and Harvard Medical School, where extensive clinical, scientific and faculty resources are available to ensure the completion of the project. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23CA115682-03
Application #
7252036
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$136,890
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Yu, Lijian; Kim, Haesook T; Kasar, Siddha et al. (2017) Survival of Del17p CLL Depends on Genomic Complexity and Somatic Mutation. Clin Cancer Res 23:735-745
Tiao, G; Improgo, M R; Kasar, S et al. (2017) Rare germline variants in ATM are associated with chronic lymphocytic leukemia. Leukemia 31:2244-2247
Wang, Lili; Shalek, Alex K; Lawrence, Mike et al. (2014) Somatic mutation as a mechanism of Wnt/?-catenin pathway activation in CLL. Blood 124:1089-98
James, Danelle F; Werner, Lillian; Brown, Jennifer R et al. (2014) Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: a multicenter clinical-translational study from the chronic lymphocytic leukemia research consortium. J Clin Oncol 32:2067-73
Rendleman, Justin; Antipin, Yevgeniy; Reva, Boris et al. (2014) Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma. PLoS One 9:e101685
Brown, Jennifer R (2013) Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials. Curr Hematol Malig Rep 8:1-6
Davids, Matthew S; Brown, Jennifer R (2013) Phosphoinositide 3'-kinase inhibition in chronic lymphocytic leukemia. Hematol Oncol Clin North Am 27:329-39
Brown, Jennifer R; Messmer, Bradley; Werner, Lillian et al. (2013) A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Haematologica 98:964-70
Improgo, Ma Reina; Brown, Jennifer R (2013) Genomic approaches to chronic lymphocytic leukemia. Hematol Oncol Clin North Am 27:157-71
Vijai, Joseph; Kirchhoff, Tomas; Schrader, Kasmintan A et al. (2013) Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies. PLoS Genet 9:e1003220

Showing the most recent 10 out of 29 publications