Characterizing the Role of 1p36 Deletion in Breast Cancer and Identifying Candidate Tumor Suppressors; Annual summary 1 Apr 2007-31 Mar 2008

摘要

Over 60% of human breast tumors display a deletion of one copy of the 1p36 region of the short arm of chromosome 1. Tumors with this deletion show a three-fold increase in mortality, suggesting a biological role for this deletion in tumor development, and suggesting the presence of one or more tumor suppressors in this region. Purpose: Characterization of the unique biology of tumors with 1p36 deletion, and characterization of the tumor suppressor(s) in the region may inform therapeutic strategies, and present unique therapeutic targets for this subset of breast cancer cases with relatively poor survival. Scope: The goals of this research project are to (1) develop a mouse model for 1p36 deletion in breast cancer by generating mice harboring loxP sequences flanking the deletion region, and crossing to tissue-specific Cre expressing mice, (2) perform in-vivo insertional mutagenesis in breast tumors using the two- component Sleeping Beauty transposon system (mutagenic transposons mobilized by a trans-acting transposase) to tag tumor suppressors and oncogenes during tumor development and (3) to combine these two systems to identify tumor suppressors in the 1p36 region. To date, we have modified targeting constructs, generated cohorts of mice for insertional mutagenesis, identified transposon insertion sites, and developed in vitro, transplant-based alternative approaches.