Genomic Instability at Premalignant and Early Stages of Breast Cancer Development

摘要

As a continuation of our original allelotypic studies, we have determined that allelic imbalances and losses affecting the chromosome 16q arm constitute early abnormalities in breast carcinogenesis since we observed them in a significant number of preinvasive lesions. The most common region of overlapping allelic losses spans the region 16q23.3 - q24. 1, observed affected in 60 - 70% of in situ breast lesions. Positional cloning strategies are currently being employed to clone the target genes for such anomalies. We have defined approximately 300 kb of a homozygous deletion within the region q23.3 - q24.1 of chromosome 16 in a breast cancer cell line. We have mapped to this region a large number previously reported ESTs. Several new cDNA clones were isolated and mapped. We sequenced almost 400,000 DNA base pairs from the region of interest and identified numerous putative exons. We identified and are currently characterizing a gene (WWOXID) that maps to this region. The characterization of this gene as well as other potential targets and determining their role in breast carcinogenesis could lead to development of biomarker tools of diagnostic-prognostic significance.