Hyperplastic polyposis syndrome:: Phenotypic presentations and the role of MBD4 and MYH
Hyperplastic polyposis syndrome:: Phenotypic presentations and the role of MBD4 and MYH
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DOI：
10.1053/j.gastro.2006.03.046
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发表时间：
2006-07-01
期刊：
影响因子：
29.4
通讯作者：
Macrae, Finlay
中科院分区：
文献类型：
--
作者：
Chow, Elizabeth;Lipton, Lara;Macrae, Finlay
背景和目的：增生性息肉病综合征（HPS）的表型定义为多发性、大的和/或近端增生性息肉。尚无已知的种系易感性。我们的目的是描述 38 例 HPS 患者的临床病理特征，并探讨碱基切除修复基因 MBD4 和 MYH 种系突变的作用。方法：利用皇家墨尔本医院肠癌监测服务和家族癌症诊所的临床数据库，招募了 38 名 HPS 患者。对患者的首次诊断年龄、增生性息肉病的特征、息肉病和结直肠癌 (CRC) 家族史、共存腺瘤、锯齿状腺瘤、CRC 发生率以及肿瘤中的微卫星不稳定性进行分析。进行MBD4和MYH的突变分析。结果：锯齿状腺瘤很常见（26%），38 名患者中有 19 名（50%）的一级亲属患有 CRC。 HPS家族史并不常见，仅发现2例。 10 名患者出现结直肠癌，3 名患者因息肉病需要手术。在27名接受测试的患者中，未检测到MBD4致病性突变，但鉴定出6个功能意义不确定的单核苷酸多态性。在 I 患者中检测到致病性双等位基因 MYH 突变。结论：MBD4 突变不太可能与 HPS 有关；应研究 MYH 突变，尤其是当同一患者发生腺瘤时。这项研究的临床、组织病理学和分子发现应有助于我们了解 HPS 及其与锯齿状肿瘤途径的关系。
Background & Aims: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. Methods: Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. Results: Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in I patient. Conclusions: Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway.