This study was performed in a double-blind fashion, meaning that neither the patients nor the members of the research study team will know if the patient was taking sulindac or placebo until the end of the study. The Johns Hopkins scientists whose research led to the first blood tests for colon cancer predisposition have now developed a technology that dramatically improves the accuracy of such tests. Now, we can tell people who seek testing with much greater certainty whether or not they have inherited specific genetic predispositions to colon cancer. The team from The Johns Hopkins Oncology Center and the Howard Hughes Medical Institute overcame a major obstacle to testing for genetic mutations in inherited diseases by unmasking mutated genes. The new technology, called conversion, takes advantage of what has long been a weakness in genetic testing.
Normal genes can mask or hide defective ones.
Conventional genetic tests analyze both copies of potentially mutated genes at the same time. Conversion separates the two copies of the gene, allowing them to be individually analyzed. With current tests, if a portion of a gene was deleted, that deletion mutation could be masked or hidden by the normal copy of the gene. Researchers uncovered masked mutant genes by fusing human cells with specially designed mouse cells to create mouse-human cell lines. Each cell line contained a copy of the gene they wanted to study.