文章：

寻找肾细胞癌的遗传原因

Searching for the hereditary causes of renal-cell carcinoma

原文发布日期：2004-05-01

DOI: 10.1038/nrc1364

类型: Review Article

开放获取: 否

要点：

1. A predisposition to renal cancer has been identified in several autosomal-dominant inherited cancer syndromes.
2. von Hippel–Lindau (VHL) disease, associated with conventional (clear-cell) renal-cell carcinomas and multi-organ neoplasia, is caused by germline mutations in the VHL tumour-suppressor gene and loss of the wild-type VHL allele.
3. Patients with hereditary papillary renal carcinoma (HPRC) harbour germline-activating mutations in the MET proto-oncogene, which can cause renal cancers with papillary type-1 histology.
4. Papillary type-2 renal carcinomas and cutaneous and uterine smooth-muscle tumours are associated with the syndrome of hereditary leiomyomatosis and renal-cell cancer (HLRCC), which is caused by germline loss-of-function mutations in the fumarate-hydratase (FH) gene.
5. The Birt–Hogg–Dubé syndrome (BHD) predisposes to cutaneous nodules (benign tumours of the hair follicle), spontaneous pneumothorax and an increased risk for renal cancers of various histological types, such as chromophobe renal-cell carcinoma and oncocytic hybrid renal tumour. BHD is caused by germline mutations in a newly discovered tumour-suppressor gene, BHD.
6. Hyperparathyroidism-jaw tumour syndrome (HPT-JT) is associated with parathyroid adenomas, fibro-osseous tumours of the jaw, and unusual renal tumours containing a mixture of epithelial and stromal elements. This syndrome is caused by germline mutations in HRPT2.
7. The identification of non-VHL families affected with clear-cell renal carcinomas, termed familial clear-cell renal carcinoma (FCRC), indicates that additional renal-cancer-predisposing genes remain to be identified.
8. Diagnosis and appropriate treatment of these hereditary renal-cancer-associated syndromes relies on an understanding of their clinical spectrum, accurate histological evaluation of renal tumours from patients and on genetic testing for predisposing genes.

要点翻译：

1. 肾癌的易感性已在多种常染色体显性遗传性癌症综合征中得到确认。
2. von Hippel-Lindau（VHL）病与经典型（透明细胞）肾细胞癌和多器官肿瘤形成相关，由VHL肿瘤抑制基因的种系突变和野生型VHL等位基因的缺失引起。
3. 遗传性乳头状肾细胞癌（HPRC）患者携带MET原癌基因的种系激活突变，这可导致具有乳头状1型组织学特征的肾癌。
4. 乳头状2型肾细胞癌以及皮肤和子宫平滑肌肿瘤与遗传性平滑肌瘤病和肾细胞癌（HLRCC）综合征相关，该综合征由延胡索酸水合酶（FH）基因的种系功能丧失性突变引起。
5. Birt-Hogg-Dubé综合征（BHD）易导致皮肤结节（毛囊良性肿瘤）、自发性气胸以及多种组织学类型肾癌（如嫌色细胞肾细胞癌和嗜酸细胞混合性肾肿瘤）的风险增加。BHD由新发现的肿瘤抑制基因BHD的种系突变引起。
6. 甲状旁腺功能亢进-颌骨肿瘤综合征（HPT-JT）与甲状旁腺腺瘤、颌骨纤维骨性肿瘤以及包含上皮和间质成分混合物的罕见肾肿瘤相关。该综合征由HRPT2基因的种系突变引起。
7. 非VHL家族罹患透明细胞肾癌（称为家族性透明细胞肾癌，FCRC）的发现表明，仍有其他肾癌易感基因有待识别。
8. 这些遗传性肾癌相关综合征的诊断和适当治疗，有赖于对其临床谱系的了解、对患者肾肿瘤的精确组织学评估以及对易感基因的遗传学检测。

英文摘要：

Families with hereditary predispositions to cancer continue to provide a unique opportunity for the identification and characterization of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal-cell carcinoma, and already genes associated with five of these syndromes have been identified — VHL, MET, FH, BHD and HRPT2. These very different genes and the biochemical pathways in which they participate raise interesting questions about the development of renal cancers and could lead to new therapeutic approaches in the near future. So, what is known about hereditary renal cancer at present?

摘要翻译： 

具有癌症遗传倾向的家庭仍为识别和表征参与肿瘤发生的基因提供独特机会。令人惊讶的是，大量遗传综合征易诱发肾细胞癌，其中与五种综合征相关的基因已被鉴定——VHL、MET、FH、BHD 和 HRPT2。这些差异显著的基因及其参与的生化通路，引发关于肾癌发展的有趣问题，并可能在不远的将来带来新的治疗策略。那么，目前对遗传性肾癌有何认识？

原文链接：

Searching for the hereditary causes of renal-cell carcinoma