{"entity":{"id":"tfe3-rearranged-renal-cell-carcinoma","kind":"cancer","name":"TFE3-rearranged (translocation) renal cell carcinoma","aka":["Translocation renal cell carcinoma","Xp11 translocation renal cell carcinoma","MiT family translocation renal cell carcinoma","TFE3-translocation RCC","TFEB-altered renal cell carcinoma","Translocation (TFE3/TFEB)","Translocation Renal Cell Carcinoma"],"tldr":"Translocation renal cell carcinoma is a rare kidney cancer, more often seen in children and young adults, driven by a rearrangement of the TFE3 gene (or its relative TFEB). It can look like clear cell or papillary kidney cancer under the microscope, so it is found by testing for the gene. There is no standard treatment for advanced disease, which is treated with the usual kidney cancer drugs.","summary":"The 2022 WHO classification groups TFE3-rearranged and TFEB-altered (rearranged or amplified) renal cell carcinomas as the molecularly defined MiT family translocation carcinomas (Moch 2022). TFE3-translocation carcinoma is highly heterogeneous clinically and genetically: among 63 untreated primaries studied by whole-exome and RNA sequencing, the ASPSCR1-TFE3 fusion and copy-number changes including loss of 22q went with aggressive features and poor outcome, most tumours (except MED15-TFE3) showed low PD-L1 expression and low T-cell infiltration, and five transcriptional clusters with distinct angiogenesis, stroma, proliferation and KRAS-down signatures tracked with fusion type and prognosis (Nature Communications 2021). A mouse model expressing PRCC-TFE3 in the kidney reproduced the histology, showed elevated RET expression that the RET inhibitor vandetanib suppressed, and identified GPNMB as a diagnostic marker (Molecular Cancer Research 2019).\n\nHow it differs from its parent: it is defined by a fusion rather than by VHL loss, occurs at a younger age, is misdiagnosed as clear cell or papillary carcinoma without TFE3 immunohistochemistry or FISH, and lacks the immune-rich microenvironment that makes clear cell carcinoma respond to checkpoint inhibitors.\n\nHow common: no registry share was found in the sources read.\n\nTreatment: surgery for localised disease; for advanced disease there is no standard, and the VEGF-directed and checkpoint combinations of the renal cell carcinoma page are used with retrospective evidence only (Nature Communications 2021). A registry trial of agnostic therapy in rare solid tumours lists translocation renal cell carcinoma among its conditions.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Renal_cell_carcinoma","links":[{"label":"NCI PDQ: renal cell cancer treatment","url":"https://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq"},{"label":"Moch 2022, European Urology: the 2022 WHO classification of urinary and male genital tumours, part A (renal, penile, testicular)","url":"https://doi.org/10.1016/j.eururo.2022.06.016"},{"label":"Nature Communications 2021: integrated exome and RNA sequencing of 63 TFE3-translocation renal cell carcinomas","url":"https://doi.org/10.1038/s41467-021-25618-z"},{"label":"Molecular Cancer Research 2019: TFE3 Xp11.2 translocation RCC mouse model and GPNMB as a diagnostic marker","url":"https://doi.org/10.1158/1541-7786.mcr-18-1235"}],"tags":["subtype-page","wave4","kidney","rare"],"related":["rcc","clear-cell-rcc","papillary-rcc","wilms-tumor","renal-medullary-carcinoma"],"cancers":[],"sections":[],"technologies":[],"targets":["tfe3"],"drugs":["cabozantinib","sunitinib","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06638931"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"Rare, and commonest in children and young adults; the largest molecular series holds 63 untreated primary tumours (Nature Communications 2021). No registry share was found in the sources read.","subtypes":["TFE3-rearranged renal cell carcinoma with ASPSCR1-TFE3 fusion (aggressive)","TFE3-rearranged renal cell carcinoma with PRCC-, SFPQ-, NONO- or MED15-TFE3 fusion","TFEB-rearranged renal cell carcinoma (t(6;11); indolent)","TFEB-amplified renal cell carcinoma (aggressive)","Translocation carcinoma resembling clear cell or papillary renal cell carcinoma on morphology"],"biomarkers":["TFE3 or TFEB rearrangement by FISH or RNA sequencing; TFE3 immunohistochemistry","Fusion partner (ASPSCR1 versus others) and 22q loss (prognostic)","Cathepsin K and melanocytic markers (Melan-A, HMB45)","GPNMB expression (research marker)"],"standardOfCare":[{"setting":"All stages","approach":"Surgery when localised; advanced disease treated on the renal cell carcinoma page's VEGF and checkpoint pathways without a dedicated standard.","refs":["rcc","cabozantinib","sunitinib","nivolumab"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"rcc"},"route":"/cancers/tfe3-rearranged-renal-cell-carcinoma/","neighbours":{"cancer":[{"id":"clear-cell-rcc","kind":"cancer","name":"Clear cell renal cell carcinoma","route":"/cancers/clear-cell-rcc/"},{"id":"collecting-duct-carcinoma","kind":"cancer","name":"Collecting duct carcinoma of the kidney","route":"/cancers/collecting-duct-carcinoma/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"renal-medullary-carcinoma","kind":"cancer","name":"Renal medullary carcinoma (SMARCB1-deficient)","route":"/cancers/renal-medullary-carcinoma/"},{"id":"wilms-tumor","kind":"cancer","name":"Wilms tumour (nephroblastoma)","route":"/cancers/wilms-tumor/"}],"target":[{"id":"tfe3","kind":"target","name":"TFE3","route":"/targets/tfe3/"}],"drug":[{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"sunitinib","kind":"drug","name":"Sunitinib","route":"/drugs/sunitinib/"}],"trial":[{"id":"nct06638931","kind":"trial","name":"Agnostic Therapy in Rare Solid Tumors","route":"/trials/nct06638931/"}]}}