克利夫兰研究人员已发现增加甲状腺癌风险的三个基因，这种癌症在男性和女性中均有最大的发病率增加。
研究由Charis Eng博士领导，他是院克利夫兰临床勒纳研究院基因组医学所的主席与创始主任，包括近3000例患Cowden综合征（CS）或CS样疾病的病人，该病与乳腺癌和甲状腺癌的风险性增高相关。
PTEN基因的突变是Cowden综合征的基础。PTEN是一个肿瘤抑制基因，有助于指示细胞生长和分化。在约80%的Cowden综合征病人中，发现PTEN基因的遗传突变。这些突变阻止PTEN蛋白有效地调换细胞存活与分化，这能导致肿瘤形成。
"我们对甲状腺疾病背后的遗传学研究提出与诊断和治疗相关的重要联系"，Eng博士说，"我们希望促进最早期诊断与最具针对性治疗的可能性。"
这项研究的结论发表在《临床内分泌学与代谢杂志》(Journal of Clinical Endocrinology & Metabolism)上，发现18岁以下的6个病人均有病原性PTEN突变。研究人员推荐具有引起CS相关疾病的PTEN突变的孩子甲状腺应该接受加强监护。
患甲状腺癌的孩子被推荐做PTEN突变测试，这个测试可担保其他癌症或疾病的监护。相反，SDH基因与KLLN基因改变与儿童甲状腺癌无关。
在确定遗传咨询中的PTEN基因测试已经常规地实行，也是一个个性化临床筛查与治疗的强大的能化基因诊断测试。一旦SDH和KLLN发现被独立地证实，这个测试就能作为临床常规测试。重要的是，这三个基因属于不同的细胞通路，以便于根据哪一个基因参与而采用特定的分子靶向治疗。（生物谷bioon.com）
doi:10.1210/jc.2011-1616
PMC:
PMID:
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
Joanne Ngeow, Jessica Mester, Lisa A. Rybicki, Ying Ni, Mira Milas and Charis Eng
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 < 0.001] for pathogenic PTENmutations, 63 (95% CI, 42-92; P < 0.001) for SDHx variants, and 45 (95% CI, 26-73; P < 0.001) for KLLN epimutations. All six (16.7%) diagnosed under age 18 yr carried pathogenic PTENmutations. 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 PTENpathogenic mutations and of papillary thyroid cancer from SDHx and KLLN alterations. Children presenting with thyroid cancer should be tested for PTEN mutations.
