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Profiling of Cancer Genes May Lead to Earlier Detection Human Cancers

A research team at UT Southwestern Medical Center has for the first time identified several genes// whose expression is lost in four of the most common solid human cancers – lung, breast, prostate and colon cancer.

The expression of genes that inhibit cancer development, so-called tumor suppressor genes, is often lost in tumor cells. This can occur through a mutation in the gene’s DNA sequence or through deletion of the gene. Loss of tumor suppression function also can occur in a process called methylation, where a chemical called a methyl group is attached to a DNA region near the gene and prevents it from being activated, essentially “silencing” the gene.

“These results show the power of studying tumors on a genome-wide basis, looking at many genes at the same time,” said Dr. John Minna, the study’s senior author and director of the W.A. “Tex” and Deborah Moncrief Jr. Center for Cancer Genetics and the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research at UT Southwestern.

In an effort to identify new tumor-suppressor genes that might be important to lung and breast cancer development, the UT Southwestern team examined which genes are active in those kinds of tumors and compared them to gene expression profiles from normal lung epithelial cells. The researchers then examined the gene expression profiles of these various cell types before and after treatment with a drug that inhibits methylation.

The researchers identified approximately 130 genes that may be methylated and thus silenced in lung, breast, prostate and colon cancers. They analyzed 45 of these new genes in both normal and cancerous tissues from the same patients and found that many of the genes were methylated specifically in the tumor samples.

“We ended up with a large number of genes that are involved in the development of lung cancer that, despite years of work in the field, I had never connected to lung cancer before,” sai
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