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• W2004134400 startingPage "E2063" @default.
• W2004134400 abstract "Abstract Context: Thyroid cancer is believed to be an important component of Cowden syndrome (CS). Germline PTEN and SDHx mutations and KLLN epimutation cause CS and CS-like phenotypes. Despite the established association, little is known about the incidence and clinical features of thyroid cancer found in CS/CS-like patients. Objective: The aim of the study was to compare incidence, clinical, and histological characteristics of epithelial thyroid cancers in CS/CS-like individuals, in the context of PTEN, SDHx, and KLLN status. Design and Participants: The study encompassed a 5-yr, multicenter, prospective accrual of 2723 CS and CS-like patients, all of whom had comprehensive PTEN analysis. SDHx mutation analysis occurred in those without PTEN mutations/variations and elevated manganese superoxide dismutase (MnSOD) levels. KLLN epimutation analysis was performed in the subset without any PTEN or SDHx mutation/deletion/ variant/polymorphism. Main Outcome Measures: Gene-specific thyroid cancer histologies, demographic and clinical information, and adjusted standardized incidence rates were studied. Results: Of 2723 CS/CS-like patients, 664 had thyroid cancer. Standardized incidence rates for thyroid cancer were 72 [95% confidence interval (CI), 51–99; P &lt; 0.001] for pathogenic PTEN mutations, 63 (95% CI, 42–92; P &lt; 0.001) for SDHx variants, and 45 (95% CI, 26–73; P &lt; 0.001) for KLLN epimutations. All six (16.7%) diagnosed under age 18 yr carried pathogenic PTEN mutations. Follicular thyroid cancer was overrepresented in PTEN mutation-positive cases compared to those with SDHx and KLLN alterations. PTEN frameshift mutations were found in 31% of patients with thyroid cancer compared to 17% in those without thyroid cancer. Conclusions: CS/CS-like patients have elevated risks of follicular thyroid cancer due to PTEN pathogenic mutations and of papillary thyroid cancer from SDHx and KLLN alterations. Children presenting with thyroid cancer should be tested for PTEN mutations." @default.
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• W2004134400 date "2011-12-01" @default.
• W2004134400 modified "2023-10-11" @default.
• W2004134400 title "Incidence and Clinical Characteristics of Thyroid Cancer in Prospective Series of Individuals with Cowden and Cowden-Like Syndrome Characterized by Germline PTEN, SDH, or KLLN Alterations" @default.
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• W2004134400 doi "https://doi.org/10.1210/jc.2011-1616" @default.
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