Identification and Characterization of Molecular Abnormalities of 11p Genes in Human Breast Cancer
Annual rept. 1 Oct 96-30 Sep 97
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
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Our goat is to identify and characterize a breast cancer suppressor gene on lip15. Indirect evidence suggests that this gene is lost in half of breast cancers that metastasize and thus plays a specific role in breast cancer metastasis. We have defined the region of chromosome loss in tumors, and we are identifing candidate genes within this region and analyzing them for mutations in breast cancer, using several approaches. We have identified three separate candidate genes within this region. These include NUP98, which shows a rare sequence variation in the germline of a breast cancer patient, not seen in 200 normal control patients. A second gene we identified is a novel homologue of Rb-associated protein 48. A third gene is a novel homologue of a gene involved in fas and fasL- mediated apoptosis, which is defective in breast cancer. We have also identified a novel mechanism by which breast cancers generate and undergo abnormal gene expression, namely aberrant splicing in the absence of mutations in the target genes themselves.
- Anatomy and Physiology
- Stress Physiology