Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers

被引:240
作者
Kauffman, Eric C. [1 ]
Ricketts, Christopher J. [1 ]
Rais-Bahrami, Soroush [1 ]
Yang, Youfeng [1 ]
Merino, Maria J. [2 ]
Bottaro, Donald P. [1 ]
Srinivasan, Ramaprasad [1 ]
Linehan, W. Marston [1 ]
机构
[1] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA
[2] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA
关键词
MICROPHTHALMIA TRANSCRIPTION FACTOR; BETA-INDUCED TRANSCRIPTION; LOOP-HELIX PROTEIN; RENAL-CARCINOMA; CLINICOPATHOLOGICAL FEATURES; NUCLEAR-LOCALIZATION; TRANSLOCATION X-1; GERMLINE MUTATION; SMAD PROTEINS; UP-REGULATION;
D O I
10.1038/nrurol.2014.162
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Despite Ready two decades passing since the discovery of gene fusions involving TFE3 or TFEB in sporadic renal cell carcinoma (RCC), the molecular mechanisms underlying the renal-specific tumorigenesis of these genes remain largely unclear. The recently published findings of The Cancer Genome Atlas Network reported that five of the 416 surveyed clear cell RCC tumours (1.2%) harboured SFPQ-TFE3 fusions, providing further evidence for the importance of gene fusions. A total of five TFE3 gene fusions (PRCC-TFE3, ASPSCR1-TFE3, SFPQ-TFE3, NONO-TFE3, and CLTC-TFE3) and one TFEB gene fusion (MALAT1-TFEB) have been identified in RCC tumours and characterized at the mRNA transcript level. A multitude of molecular pathways well-described in carcinogenesis are regulated in part by TFE3 or TFEB proteins, including activation of TGF beta and ETS transcription factors, E-cadherin expression, CD4OL-dependent lymphocyte activation, mTORC1 signalling, insulin-dependent metabolism regulation, folliculin signalling, and retinoblastoma-dependent cell cycle arrest. Determining which pathways are most important to RCC oncogenesis will be critical in discovering the most promising therapeutic targets for this disease.
引用
收藏
页码:465 / 475
页数:11
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