Characterization of Novel Genes With 8p11-12 Amplicon in Breast Cancer
Annual summary 1 Jun 2003-31 May 2004
MICHIGAN UNIV ANN ARBOR
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Gene amplification plays an important role in tumorigenesis of human neoplasia, including breast cancer. Oncogenes, such as ERBB2 , CCND1 and C-MYC have already been identified as amplification targets associated with development, progression, or metastasis of breast cancer1-4. However there are several amplified regions where target genes have yet to be characterized. One of these is the 8p11-p12 region, which has been shown to be amplified in about 10-15 of human breast cancer HBC. Using chromosome comparative genomic hybridization CGH and array CGH, overlapping amplicons were found to be centered around chromosome 8p11-p12 in 3 breast cancer cell lines developed in Dr. Ethiers laboratory, SUM-44, SUM-52 and SUM-225. Thus, these 3 breast cancer cell lines are ideally suited for studies aimed at developing a better understanding of this genomic region in HBC, and for identifying and characterizing novel candidate oncogenes present at these loci. We have used fluorescence in situ hybridization FISH, Southern blot analysis, northern blot analysis, and chromosome 8-specific cDNA array to map this amplicon in the three cell lines, and identified several novel candidate genes including TC-1 C8ORF4, FLJ14299 and othersS. TC-I is a novel gene highly expressed in thyroid cancer and some fraction of breast cancers. FLJl4299 contains a C2112-like motif, which is also present in several tumor-related genes. Aberrant expression of TC-1 and FLJ14299 could be related to development and progression in breast cancer. The specific aims as outlined in this proposal will help us to better understand the biological function and genetic pathway of new target genes of this amplicon and identify better prognostic and predictive markers for an important subset of breast cancer.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research