Vogelstein & Colon Cancer

Bert Vogelstein, M.D., is a world-renowned cancer biologist and researcher with the Johns Hopkins University School of Medicine. After practicing as an oncologist for years, Dr. Vogelstein decided to pursue cancer research. His specialty is the study of colon cancer and colorectal tumors. In particular, his research has focused on the role of genetics and tumor suppressors in colon cancer.

Tumor Suppressors

• Dr. Vogelstein began his research searching for evidence of a tumor-suppressing gene whose specific function was to act as a molecular brake, slowing the growth of normal cells. He believed that colon cancer was a result of the loss of this gene, which allowed for the rapid growth of diseased cells. He found that cancer cells frequently contain chromosomes that are defective, and began searching these broken chromosomes for evidence of the tumor-suppressing gene. In this search he discovered gene p53.

Gene p53

• Gene p53 had already been investigated by other researchers who thought it functioned as an oncogene, a gene that switches on in colon cancer, not one that turns off. Dr. Vogelstein theorized that if p53 were truly a tumor suppressor, then both of its copies (one gene from each parent) would have to be "turned off" for a tumor to grow. Vogelstein and his colleagues collected cells from a colorectal tumor that had lost one copy of the p53 gene. They discovered that in every case, the other copy contained a mutation, which effectively shut down the gene's ability to suppress tumors. This mutation was never evident in cancer-free people.

Stability Genes

• Dr. Vogelstein and his fellow researchers are also studying a group of genes called stability genes, which control the rate of mutation of other genes. When these genes are genetically altered, the cell accumulates mutations at a high rate, and colon-tumor growth is accelerated. Some stability genes that they have discovered to be important in colon cancer are MSH2 and MSH6 (known as "mismatch repair genes") and BUBR1, whose alteration can cause large chromosomal abnormalities.

APC Pathways

• Dr. Vogelstein has also studied the mutations in adenomatous polypsis coli (APC) pathways that lead to colon tumors. The proteins made by this tumor-suppressing gene determine if a cell will become a tumor. Patients with inherited APC mutations will most likely develop benign colon tumors; Vogelstein is studying how other mutations interact to turn these into cancerous tumors. He has already developed a highly sensitive blood test to identify patients with the inherited APC mutations as well as the aforementioned mismatch repair genes.

Hope for Cures

• The genetic tests developed by Dr. Vogelstein and his staff as a result of his research can identify family members who have a predisposition to the hereditary forms of colorectal cancer. When combined with genetic counseling and close monitoring by an oncologist, these diagnostic tests can give families peace of mind and lead to early detection of colorectal cancers.

  Dr. Vogelstein believes that deaths from colorectal cancers can almost always be prevented if they are detected before metastasis (cancer spread) occurs. He has developed a test that can efficiently search tens of thousands of DNA molecules for mutations in the APC and other genes, called BEAMing (for beads, emulsions, amplifications, magnetics--the four components of the test).

  Dr. Vogelstein is also using his genetic research to develop new, highly effective chemotherapy treatments for both early and advanced colon cancer that prevent mutations along the genetic pathways.