title: Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers.
abstract: Despite nearly 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 TGFβ and ETS transcription factors, E-cadherin expression, CD40L-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.
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Kauffman
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ricketts
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: Soroush
authors.initials: S
authors.lastname: Rais-Bahrami
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: Youfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Bottaro
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: Ramaprasad
authors.initials: R
authors.lastname: Srinivasan
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, CRC Room 1-5940, Bethesda, MD 20892, USA.
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
mesh_terms: D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; C069203:TFE3 protein, human; C064972:TFEB protein, human