Characterization of Putative Proto-Oncogenes and Tumor Suppressor Genes that are Transcriptionally Deregulated in Breast Cancer
Annual rept. 1 Jun 1998-1 Jun 1999
MOUNT SINAI HOSPITAL TORONTO (ONTARIO)SAMUEL LUNENFIELD RESEARCH INST
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Candidate proto-oncogenes and tumor suppressor genes were previously isolated in a gene expression study involving breast cancer. The present research focus on the characterization of genetic alterations in a number of these candidate proto-oncogenes and tumor suppressor genes to understand how they may be contributing to mammary carcinogenesis. In particular, the candidate proto-oncogene CC-41LAF-4, which has a cell type specific expression, was found to be highly expressed in a third of breast tumors. A possibility remained that high CC-41LAF-4 expression resulted from infiltrating inflammatory cells, which express the gene at high levels. Histology review and in situ hybridization demonstrate that CC-41LAF-4 high expression detected in some breast tumors was tumor cell-specific. This result indicates that CC-41LAF-4 overexpression may be an important molecular genetic event during mammary tumorigenesis. Another gene isolated from the gene expression analysis was hypothesized to be a candidate tumor suppressor gene. Although presenilin-2 maps to a chromosomal region affected by LOH, analysis of presenilin-2 entire coding region has failed to detect any mutation in 60 different breast tumors. Recent development in the lab with other cancers suggests that presenilin-2 mutational analysis should target breast cancers characterized by an early age of onset. This work is currently being pursued.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research