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Certain genetic test helps detect mutations that may be missed by conventional DNA test

Researchers have identified a genetic test that when used with DNA testing would detect a higher number of genetic mutations in colorectal cancer patients, according to a study in the February 16 issue of JAMA, a theme issue on medical applications of biotechnology.

Hereditary nonpolyposis colorectal cancer (HNPCC) has historically been diagnosed based on family history, according to background information in the article. Approximately 70 percent of HNPCC cases and a proportion of cases that do not fit these criteria can be accounted for by mutations in any one of several genes involved in DNA mismatch repair (a mechanism that corrects errors made during DNA replication). Identification of a mutation may prompt genetic counseling, screening, and surveillance of relatives to reduce illness and risk of death. It has been proposed that screening of all patients with colorectal cancer for mismatch repair gene mutations may be both feasible and desirable.

"The accurate identification and interpretation of mismatch repair mutation carriers is essential for clinical management of colorectal cancer patients and for scientific studies in which the mutation status of participants is an important variable. Currently, most genetic testing is performed by genomic DNA sequence analysis, but certain classes of gene mutations are not detected using this approach, " the authors write.

There is evidence that large genomic mutations may account for a substantial proportion of colorectal cancer cases. Recent studies have suggested that conversion analysis, in which human chromosomes are separated in hybrids prior to mutation screening, represents a more sensitive mutation detection method than conventional DNA sequencing for identifying such mutations. There have been no studies comparing the relative accuracy and specificity of conversion analysis with other mutation testing methods in a rigorous way, which is essential if the method is to be widely used clini
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Contact: Lisa Murphy
216-444-7935
JAMA and Archives Journals
15-Feb-2005


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