Hereditary leiomyomatosis and renal cell carcinoma.
Hereditary leiomyomatosis and renal cell carcinoma.
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DOI：
10.2147/ijnrd.s42097
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发表时间：
2014
影响因子：
2
通讯作者：
Linehan WM
中科院分区：
文献类型：
--
作者：
Schmidt LS;Linehan WM
遗传性平滑肌瘤病和肾细胞癌（HLRCC）是一种常染色体显性遗传综合征，由编码三羧酸循环酶富马酸水合酶（FH）的FH基因的种系突变引起。HLRCC患者易发生皮肤平滑肌瘤，年轻女性多发、有症状的子宫肌瘤，导致早期子宫切除术，以及早发性肾肿瘤，2型乳头状形态，即使很小也可进展和转移。由于与hlrc相关的肾肿瘤比其他遗传性肾癌综合征的肾肿瘤更具侵袭性，因此需要谨慎，建议手术干预而不是主动监测。家族生殖系FH突变检测呈阳性的高危HLRCC家族成员应从8岁起每年接受磁共振成像监测。生化研究表明，fh缺乏肾癌的特征是代谢转变为有氧糖酵解。希望通过正在进行的评估靶向分子疗法的临床试验，能够开发出一种有效的治疗hlrcc相关肾癌的方法，从而改善hlrcc相关肾癌患者的预后。
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal-dominant hereditary syndrome, which is caused by germline mutations in the FH gene that encodes the tricarboxylic acid cycle enzyme fumarate hydratase (FH). HLRCC patients are predisposed to develop cutaneous leiomyomas, multiple, symptomatic uterine fibroids in young women resulting in early hysterectomies, and early onset renal tumors with a type 2 papillary morphology that can progress and metastasize, even when small. Since HLRCC-associated renal tumors can be more aggressive than renal tumors in other hereditary renal cancer syndromes, caution is warranted, and surgical intervention is recommended rather than active surveillance. At-risk members of an HLRCC family who test positive for the familial germline FH mutation should undergo surveillance by annual magnetic resonance imaging from the age of 8 years. Biochemical studies have shown that FH-deficient kidney cancer is characterized by a metabolic shift to aerobic glycolysis. It is hoped that through ongoing clinical trials evaluating targeted molecular therapies, an effective form of treatment for HLRCC-associated kidney cancer will be developed that will offer an improved prognosis for individuals affected with HLRCC-associated kidney cancer.