PTEN hamartoma tumor syndromes.
PTEN hamartoma tumor syndromes.
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DOI：
10.1038/ejhg.2008.162
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Dennis PA
中科院分区：
文献类型：
--
作者：
Blumenthal GM;Dennis PA
PTEN 错构瘤肿瘤综合征 (PHTS) 是一组罕见的临床综合征，其特征是肿瘤抑制基因 PTEN 种系突变。这些综合征是由细胞过度生长引起的，导致几乎任何器官出现良性错构瘤。考登综合征 (CS) 是典型的 PHTS 综合征，与乳腺癌、甲状腺癌和子宫内膜癌的易感性增加有关。 PTEN 位于染色体 10q22-23 上，通过其脂质磷酸酶活性负向调节促存活 PI3K/Akt/mTOR 通路。 PTEN 的缺失会激活该途径并导致细胞生长、迁移、增殖和存活增加。 PHTS 患者（尤其是 CS 患者）的临床管理应包括对相关恶性肿瘤进行早期和频繁的筛查、监测和预防性护理。随着对 PTEN 和 PI3K/Akt/mTOR 通路生物学了解的加深，该通路的抑制剂正在被开发为抗癌药物。这些药物可用于 PHTS 患者，目前尚无治疗选择。 PHTS 是一种常染色体显性错构瘤过度生长疾病谱，具有可变的表型表现，其特征是位于 10q22-23 的肿瘤抑制基因 PTEN 的种系突变。这些综合征包括 Cowden 综合征 (CS)、Lhermitte-Duclos 病 (LD)、Bannayan-Riley-Ruvalcaba 综合征 (BRRS) 以及可能的 Proteus 综合征 (PS)。这些综合征中已确定的种系 PTEN 突变的患病率差异很大，CS 中已确定的基因内 PTEN 突变的患病率为 80%，BRRS 的患病率为 65%，PS 的患病率低于 20%。 CS 是一种错构瘤疾病，其特征为巨头畸形、面部毛毛鞘瘤、肢端角化病、乳头状丘疹，以及发生乳腺癌、甲状腺癌和子宫内膜癌的风险增加。成人发病的 LD 被认为是 CS 的一种变体，其特征是小脑发育不良神经节细胞瘤，通常导致颅内压升高、共济失调和癫痫发作。 BRRS 的特征是男性龟头发育迟缓、大头畸形、脂肪瘤、血管瘤和色素斑。 PS 是一种复杂、快速进展的疾病，其特征为嵌合体、半肥大、皮下肿瘤以及各种骨、皮肤和血管异常。 PS 和 PTEN 突变之间的关联仍然存在争议。对易感恶性肿瘤的筛查、监测和预防护理是 PHTS 患者临床管理的支柱。由于 PTEN 的缺失会增加 PI3K/Akt/mTOR 通路的激活，因此靶向该通路的药物可能可用于治疗和/或预防与 PHTS 相关的肿瘤。
The PTEN hamartoma tumor syndromes (PHTS) are a collection of rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. These syndromes are driven by cellular overgrowth, leading to benign hamartomas in virtually any organ. Cowden syndrome (CS), the prototypic PHTS syndrome, is associated with increased susceptibility to breast, thyroid, and endometrial cancer. PTEN is located on chromosome 10q22–23 and negatively regulates the prosurvival PI3K/Akt/mTOR pathway through its lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. Clinical management of patients with PHTS, particularly those with CS, should include early and frequent screening, surveillance, and preventive care for associated malignancies. Concomitant with improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway, inhibitors of this pathway are being developed as anticancer agents. These medications could have applications for patients with PHTS, for whom no medical options currently exist. PHTS is an autosomal dominant spectrum of hamartomatous overgrowth disorders with variable phenotypic manifestations characterized by germline mutations of the tumor suppressor gene PTEN located at 10q22–23. These syndromes include Cowden syndrome (CS), Lhermitte–Duclos disease (LD), Bannayan–Riley–Ruvalcaba syndrome (BRRS), and possibly Proteus syndrome (PS). The prevalence of identified germline PTEN mutations in these syndromes varies widely, with CS having 80% prevalence of identified intragenic PTEN mutations, BRRS 65% prevalence, and PS less than 20% prevalence. CS is a hamartomatous disorder characterized by macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and an increased risk for the development of breast, thyroid, and endometrial carcinoma. Adult onset LD is considered a variant of CS characterized by dysplastic gangliocytoma of the cerebellum often leading to increased intracranial pressure, ataxia, and seizures. BRRS is characterized by the developmental delay, macrocephaly, lipomas, hemangiomas, and pigmented speckled macules of the glans penis in males. PS is a complex, rapidly progressive disorder characterized by mosaicism, hemihypertrophy, subcutaneous tumors, and various bone, cutaneous and vascular anomalies. The association between PS and PTEN mutations remains controversial. Screening, surveillance, and preventive care for susceptible malignancies are the mainstays of clinical management for patients with PHTS. Because loss of PTEN increases activation of the PI3K/Akt/mTOR pathway, drugs that target this pathway may have utility for treatment and/or prevention of tumors associated with PHTS.
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影响因子：
15.8
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
2.4
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
2
作者：
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通讯作者：
Longy, M