克利夫蘭研究人員已發(fā)現(xiàn)增加甲狀腺癌風(fēng)險(xiǎn)的三個(gè)基因，這種癌癥在男性和女性中均有最大的發(fā)病率增加,。
研究由Charis Eng博士領(lǐng)導(dǎo)，他是院克利夫蘭臨床勒納研究院基因組醫(yī)學(xué)所的主席與創(chuàng)始主任,，包括近3000例患Cowden綜合征（CS）或CS樣疾病的病人,，該病與乳腺癌和甲狀腺癌的風(fēng)險(xiǎn)性增高相關(guān)。
PTEN基因的突變是Cowden綜合征的基礎(chǔ),。PTEN是一個(gè)腫瘤抑制基因,，有助于指示細(xì)胞生長(zhǎng)和分化。在約80%的Cowden綜合征病人中,，發(fā)現(xiàn)PTEN基因的遺傳突變,。這些突變阻止PTEN蛋白有效地調(diào)換細(xì)胞存活與分化，這能導(dǎo)致腫瘤形成,。
"我們對(duì)甲狀腺疾病背后的遺傳學(xué)研究提出與診斷和治療相關(guān)的重要聯(lián)系",，Eng博士說，"我們希望促進(jìn)最早期診斷與最具針對(duì)性治療的可能性,。"
這項(xiàng)研究的結(jié)論發(fā)表在《臨床內(nèi)分泌學(xué)與代謝雜志》(Journal of Clinical Endocrinology & Metabolism)上,，發(fā)現(xiàn)18歲以下的6個(gè)病人均有病原性PTEN突變,。研究人員推薦具有引起CS相關(guān)疾病的PTEN突變的孩子甲狀腺應(yīng)該接受加強(qiáng)監(jiān)護(hù)。
患甲狀腺癌的孩子被推薦做PTEN突變測(cè)試,，這個(gè)測(cè)試可擔(dān)保其他癌癥或疾病的監(jiān)護(hù),。相反，SDH基因與KLLN基因改變與兒童甲狀腺癌無關(guān),。
在確定遺傳咨詢中的PTEN基因測(cè)試已經(jīng)常規(guī)地實(shí)行,，也是一個(gè)個(gè)性化臨床篩查與治療的強(qiáng)大的能化基因診斷測(cè)試。一旦SDH和KLLN發(fā)現(xiàn)被獨(dú)立地證實(shí),，這個(gè)測(cè)試就能作為臨床常規(guī)測(cè)試,。重要的是，這三個(gè)基因?qū)儆诓煌募?xì)胞通路,，以便于根據(jù)哪一個(gè)基因參與而采用特定的分子靶向治療,。（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.
