Mouse models for colorectal cancer (CRC) have been generated with germline mutations based on familial syndromes. It is unclear if these would be good representations of the most frequent forms of CRC, sporadic cases. Though APC mutations have been found in most tumors, there is a significant number in which this gene is unaltered. We must more clearly understand the pathways and cellular changes involved in carcinogenesis in order to develop novel clinical modalities. As such, we hypothesize that APC-independent pathways must be involved in CRC development. We propose to develop a new model for sporadic CRC using adenoviral enemas to deliver Cre recombinase to a mouse with a conditional mutation in the cancer predisposition gene Mlh1. We will use a novel approach to simultaneously inactivate Mlh1 and express GFP only in those cells exposed to Cre. Thus, we can document the natural history of the cellular events that lead to adenoma formation by following the fate of individual foci of precancerous lesions. We will characterize the genomic and gene expression changes in cells at different stages of cancer progression by array comparative genomic hybridization (aCGH) and Genechip analyses, looking for APC-independent pathways.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA110565-02
Application #
6932358
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2004-07-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$55,352
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199