文章：

癌症表型组学：RET和PTEN作为说明性模型

Cancer phenomics: RET and PTEN as illustrative models

原文发布日期：2006-12-14

DOI: 10.1038/nrc2037

类型: Review Article

开放获取: 否

要点：

1. Cancer phenomics refers to the systematic and meticulous collection, objective documentation and cataloguing of phenotypic data at many levels, including clinical, molecular and cellular phenotype. Compared with other genes that predispose to the development of cancer, robust phenomic data exists for rearranged during transfection (RET) and phosphatase and tensin homologue (PTEN).
2. Germline PTEN and RET mutations predispose to the cancer-associated syndromes Cowden syndrome (CS) and multiple endocrine neoplasia type 2 (MEN 2), respectively. Both genes also predispose to developmental disorders with seemingly disparate phenotypes.
3. CS predisposes to breast, thyroid and endometrial cancer, whereas MEN 2 predisposes to medullary thyroid cancer (MTC), phaeochromocytoma and hyperparathyroidism.
4. Phenomics has shown that germline RET and PTEN mutations are present in a subset of patients with apparently sporadic cancer involving neoplasias that are components of MEN 2 and CS, respectively. Identifying these mutations will have important implications for personalized genetic health care.
5. Meticulous characterization of RET phenomics at the clinical and biochemical levels has resulted in individualized patient management with respect to cancer surveillance and prophylactic surgery in MEN 2. In addition, phenomics offers valuable insight into the aetiology of the variable expression of features seen in MEN 2.
6. Through phenomic-based research, the spectrum of phenotypes associated with germline PTEN mutations is continually evolving, and these are collectively termed the PTEN hamartoma tumour syndromes (PHTS). Such research has also led to the continual refinement of the diagnostic criteria for CS.
7. The current opinion is that all patients with PHTS, irrespective of phenotype, follow the cancer surveillance guidelines recommended for CS. These guidelines are updated annually by the US National Comprehensive Cancer Network.
8. Molecular phenomic research has explored new mechanisms of PTEN dysfunction, including splice-site variation and the localization of PTEN to different cellular compartments.
9. Through an understanding of the PTEN–AKT pathway, and its cross-talk with other pathways important in tumorigenesis, the use of targeted therapies seems promising for the treatment of PHTS. However, these agents must be used with caution, as their effects on the development and homeostasis of normal tissue deserves careful consideration.

要点翻译：

1. 癌症表型组学是指在多个层面（包括临床、分子和细胞表型）系统而细致地收集、客观记录和分类表型数据。与其他易导致癌症发生的基因相比，转染时重排（RET）和磷酸酶与张力蛋白同源物（PTEN）基因拥有更丰富的表型组学数据。
2. 胚系PTEN和RET突变分别易导致癌症相关综合征——Cowden综合征（CS）和2型多发性内分泌腺瘤（MEN 2）。这两种基因也易导致表型明显不同的发育障碍。
3. CS易导致乳腺癌、甲状腺癌和子宫内膜癌，而MEN 2易导致甲状腺髓样癌（MTC）、嗜铬细胞瘤和甲状旁腺功能亢进。
4. 表型组学研究表明，胚系RET和PTEN突变存在于一部分看似散发性癌症患者中，这些肿瘤分别是MEN 2和CS的组成部分。识别这些突变将对个性化基因医疗具有重要意义。
5. 在临床和生化层面对RET表型组学的细致表征，已促使MEN 2患者在癌症监测和预防性手术方面实现个体化管理。此外，表型组学为了解MEN 2中特征性表达变异性的病因提供了宝贵见解。
6. 通过基于表型组学的研究，与胚系PTEN突变相关的表型谱系不断扩展，这些被统称为PTEN错构瘤肿瘤综合征（PHTS）。此类研究还促使CS的诊断标准持续完善。
7. 目前观点认为，所有PHTS患者无论表型如何，都应遵循针对CS推荐的癌症监测指南。这些指南由美国国家综合癌症网络每年更新。
8. 分子表型组学研究探索了PTEN功能障碍的新机制，包括剪接位点变异以及PTEN在不同细胞区室中的定位。
9. 通过理解PTEN-AKT通路及其与肿瘤发生中重要的其他通路之间的交叉对话，靶向治疗在PHTS治疗中展现出前景。然而，必须谨慎使用这些药物，因为它们对正常组织发育和稳态的影响值得仔细考量。

英文摘要：

Cancer phenomics, the systematic acquisition and objective documentation of host and/or somatic cancer phenotypic data at many levels, is a young field compared with other molecular-based 'omics'. Two relatively advanced phenomic paradigms are associated with phosphatase and tensin homologue (PTEN) and rearranged during transfection (RET), genes that are associated with cancer predisposition syndromes in addition to developmental disorders. The phenomic characterization of PTEN and RET underscores the importance of incorporating robust phenomics into the host 'omic' profile, and shows that the evolution of phenomics will be crucial to the advancement of personalized medicine.

摘要翻译： 

癌症表型组学是在多个层面上系统获取并客观记录宿主和/或体细胞表型数据的新兴领域，相比其他基于分子的“组学”仍处起步阶段。磷酸酶与张力蛋白同源物（PTEN）及转染重排（RET）是两个相对成熟的表型组范例，它们不仅与发育异常相关，也涉及癌症易感综合征。对PTEN与RET的表型组刻画凸显了将稳健表型组学纳入宿主“组学”档案的重要性，并表明表型组学的演进将是推进个体化医疗的关键。

原文链接：

Cancer phenomics: RET and PTEN as illustrative models