"We know that 80 percent of Cowden patients carry the PTEN mutation and half of the remaining 20 percent carry the inactive KILLIN gene," Dr. Eng said. "What that means is that altogether PTEN and KILLIN should account for 90 percent of all cases of classic Cowden syndrome, a huge step forward in diagnosing an often overlooked disease. More importantly, KILLIN and PTEN should account for almost half of CLS individuals."

This study shows that CS/CLS individuals with KILLIN promoter methylation, which switches the KILLIN gene off, have a threefold greater risk of breast cancer, and a twofold greater risk of kidney cancer, compared to those with mutant PTEN. Having the ability to identify these individuals will allow for more proactive management of their health, such as more careful screening and shared best practices among physicians who treat them.

Findings from this study indicate that individuals with classic Cowden syndrome should be offered PTEN testing first; those found not to have PTEN mutations should then be screened for the inactivated KILLIN gene and offered genetic counseling. Those patients who carry neither the PTEN mutation nor the inactive KILLIN gene should be offered additional/alternative genetic testing and importantly, encouraged to participate in research.

Source: Cleveland Clinic Foundation