KLLN epigenotype–phenotype associations in Cowden syndrome

• DOI: 10.1038/ejhg.2015.8
• Publication Date: 2015-02-11T11:14:35Z
• Authors: Emily A Nizialek; Jessica L Mester; Vineet K Dhiman; Dominic J Smiraglia; Charis Eng
• Keywords: Cowden syndrome

Germline KLLN promoter hypermethylation was recently identified as a potential genetic etiology of the cancer predisposition syndrome, Cowden syndrome (CS), when no causal PTEN gene mutation found. We screened for methylation in large prospective series CS patients and determined risk benign malignant features with increased both without mutation/variant unknown significance. In all, 1012 meeting relaxed International Consortium criteria including 261 mutation-positive patients, 187 variant-positive 564 mutation-negative well 111 population controls were assessed germline by MassARRAY EpiTYPER analysis. analyzed continuous dichotomous variable calculation phenotypic risks stepwise logistic regression Kaplan–Meier/standardized incidence ratio methods, respectively. Significantly seen individuals mutation/VUS compared (P<0.001). Patients high have all CS-associated malignancies general population. Interestingly, KLLN-associated thyroid appears to be gender status dependent. associated different phenotypes dependent on status. Furthermore, increasing is greater phenotype burden patients. particular features, which