Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics
Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics
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DOI：
10.1007/s10689-011-9428-z
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发表时间：
2011-06-01
期刊：
影响因子：
2.2
通讯作者：
Lehtonen, Heli J.
中科院分区：
文献类型：
--
作者：
Lehtonen, Heli J.
遗传性平滑肌瘤病和肾细胞癌（HLRCC，也称为多发性皮肤和子宫平滑肌瘤病，MCUL）是一种高度外显的常染色体显性肿瘤易感综合征，其特征是皮肤和子宫的良性平滑肌瘤。肾细胞癌，发生在一个子集的HLRCC家庭，是非常积极的。因此，建议采取谨慎、频繁的监测策略。恶性平滑肌肿瘤，平滑肌瘤，与HLRCC的关联已被观察到，但风险似乎比最初估计的要小。迄今为止，在全球约180个家族中发现了富马酸水合酶（FH，脱氢酶）基因的失活杂合突变，易患HLRCC。对HLRCC肿瘤发生的分子机制研究最广泛的假设是由于HIF 1转录因子的异常稳定而激活缺氧途径。HIF 1调节血管形成、葡萄糖转运和糖酵解相关基因的转录，这些过程促进肿瘤生长。然而，可能存在肿瘤形成的其他机制。
Hereditary leiomyomatosis and renal cell cancer (HLRCC, also known as multiple cutaneous and uterine leiomyomatosis, MCUL) is a highly penetrant autosomal dominant tumor predisposition syndrome characterized by benign leiomyomas of the skin and the uterus. Renal cell carcinomas, occurring in a subset of the HLRCC families, are exceptionally aggressive. Therefore careful, frequent surveillance strategies are recommended. Association of malignant smooth-muscle tumors, leiomyosarcomas, with HLRCC has been observed but the risk appears to be smaller than initially estimated. To date inactivating heterozygous mutations in the fumarate hydratase (FH, fumarase) gene, predisposing to HLRCC, have been found in approximately 180 families worldwide. The most extensively studied hypothesis on molecular mechanisms of HLRCC tumorigenesis is activation of the hypoxia pathway due to aberrant stabilization of the HIF1 transcription factor. HIF1 regulates transcription of genes relevant for vascularization, glucose transport and glycolysis, processes that facilitate tumor growth. However, additional mechanisms underlying tumor formation are likely to exist.