TFEBTFE3

TFEBTFE3 is a proposed gene fusion between TFEB and TFE3, two transcription factors in the MiTF family. Both TFEB and TFE3 encode basic helix-loop-helix leucine zipper proteins that regulate lysosome biogenesis, autophagy, and related metabolic pathways. Gene rearrangements involving TFEB or TFE3 are well described in certain cancers, notably renal cell carcinomas of Xp11 translocation type and alveolar soft part sarcoma, with fusions such as TFEB-CLTC and ASPSCR1-TFE3 reported in the literature. TFEB-TFE3 would represent a chimeric product arising from the juxtaposition of these two genes, potentially producing a transcription factor with altered activity and downstream gene expression.

The exact oncogenic potential, prevalence, and tumor spectrum of TFEB-TFE3 are not well established, and published reports, if any, are rare. The fusion remains a subject of ongoing research, and its clinical significance is not yet defined beyond the broader context of MiTF-family rearrangements.

Diagnosis would rely on molecular methods to detect the fusion, such as fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), and next-generation sequencing, often supported by immunohistochemistry showing nuclear localization of MiTF family proteins. In practice, tumors with MiTF-family translocations are classified by integrated histology, immunoprofile, and molecular data, with treatment decisions guided by tumor type and stage rather than the fusion status alone.

See also: TFEB, TFE3, Xp11 translocation renal cell carcinoma, ASPSCR1-TFE3, TFEB-CLTC.