Pathogenesis and the role of ARID1A mutation in endometriosis-related ovarian neoplasms.
Pathogenesis and the role of ARID1A mutation in endometriosis-related ovarian neoplasms.
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DOI：
10.1097/pap.0b013e31827bc24d
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发表时间：
2013-01
影响因子：
6.7
通讯作者：
Shih IeM
中科院分区：
文献类型：
--
作者：
Maeda D;Shih IeM
子宫内膜异位症相关卵巢肿瘤(ERON)是一组独特的肿瘤，因为它们与子宫内膜异位症有关，尤其是表现为卵巢子宫内膜异位囊肿(子宫内膜瘤)的子宫内膜异位症。其病因包括透明细胞癌、子宫内膜样癌和浆液性交界性肿瘤。越来越多的来自临床病理和分子研究的证据表明，大多数(如果不是全部)ERON是从子宫内膜异位囊肿上皮发展而来的，经历了肿瘤发展的不同阶段。子宫内膜异位囊内含有丰富的铁诱导的活性氧物种，被认为是诱变的，而囊性上皮长期暴露在这种微环境中有助于体细胞突变的积累，最终导致肿瘤的发展。对ERON的分子分析，包括全基因组筛选，已经确定了几种导致ARID1A、PI3K、Wnt和PP2A途径异常激活或失活的分子遗传改变。在迄今发现的所有分子遗传学变化中，ARID1A抑癌基因的失活突变在Eron中最常见。了解ERON发展过程中的分子变化和发病机制是未来转译研究的基础，目的是设计新的早期诊断测试，并确定靶向治疗的关键分子特征。
Endometriosis-related ovarian neoplasms (ERONs) are a unique group of tumors as they are associated with endometriosis, especially endometriosis presenting as an ovarian endometriotic cyst (endometrioma). ERONs include clear cell carcinoma, endometrioid carcinoma, and seromucinous borderline tumor. A growing body of evidence from both clinicopathological and molecular studies suggests that most, if not all, ERONs develop from endometriotic cyst epithelium through different stages of tumor progression. The endometriotic cyst contains abundant iron-induced reactive oxygen species which are thought to be mutagenic, and chronic exposure of cystic epithelium to this microenvironment facilitates the accumulation of somatic mutations that ultimately result in tumor development. Molecular analyses of ERONs, including genome-wide screens, have identified several molecular genetic alterations that lead to aberrant activation or inactivation of pathways involving ARID1A, PI3K, Wnt, and PP2A. Among all molecular genetic changes identified to date, inactivating mutations of the ARID1A tumor suppressor gene are the most common in ERON. Understanding the molecular changes and pathogenesis involved in the development of ERON is fundamental for future translational studies aimed at designing new diagnostic tests for early detection and identifying critical molecular features for targeted therapeutics.