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Associated with increased risk of breast, kidney cancer over PTEN mutation-positive patients

Tuesday, December 21, 2010 (Last Updated: 12/22/2010)

TUESDAY, Dec. 21 (HealthDay News) -- In patients with Cowden syndrome or Cowden-like syndrome, germline KILLIN methylation is common, and it is related to increased risks of renal and breast cancer compared with individuals who are PTEN mutation-positive, according to research published in the Dec. 22/29 issue of the Journal of the American Medical Association.

Kristi L. Bennett, Ph.D., of the Cleveland Clinic, and colleagues analyzed nucleic acids in 123 patients with Cowden syndrome or Cowden-like syndrome and 50 unaffected subjects, none of whom had PTEN variants, for germline methylation and expression of PTEN or KILLIN. The purpose of the study was to see if germline methylation occurred in Cowden syndrome or Cowden-like syndrome in subjects who did not have PTEN mutations.

The researchers found that 45 of the 123 patients had hypermethylation upstream of PTEN, but did not show transcriptional repression. Germline methylation transcriptionally down-regulated KILLIN by 250-fold and disrupted TP53 activation of KILLIN by 30 percent. Those with KILLIN-promoter methylation had three times the prevalence of breast cancer and more than twice the number of kidney cancers than those with germline PTEN mutations.

"Germline KILLIN methylation is common among patients with Cowden syndrome or Cowden-like syndrome and is associated with increased risks of breast and renal cancer over PTEN mutation-positive individuals. These observations need to be replicated," the authors write.

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Specialties Gastroenterology
Hematology & Oncology

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