| Entity | t(X;1)(p11.2;q21.2) in renal cell carcinoma --> PRCC/TFE3 |
| Prognosis | overall 5-yr survival rate around 85% |
| Hybrid/Mutated Gene | 5' PRCC- 3' TFE3; variable breakpoint in PRCC; breakpoint in the 1st intron of TFE3 |
| Abnormal Protein | N-term PRCC with the proline rich sequence fused to most of TFE3, including the acidic transcriptional activation domain, the helix-loop-helix, and the leucine zipper; the reciprocal TFE3-PRCC is expressed; it is to be noted that the normal TFE3 transcript is lost in female patients |
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| Oncogenesis | PRCCTFE3 appears to be the fusion product that is most critical for the development of papillary renal cell carcinomas; it is a three-fold better transactivator than wild-type TFE3 and shows the characteristics associated with malignant trannsformation |
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| Entity | t(X;1)(p11.2;p34) in renal cell carcinoma --> PSF/TFE3 |
| Disease | t(X;1)(p11.2;p34) has only been found in a handfull cases of papillary renal cell carcinoma |
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| Hybrid/Mutated Gene | 5' PSF- 3' TFE3 |
| Abnormal Protein | N-term PSF and most of it fused to the DNA binding domains of TFE3 (excluding the acidic transcriptional activation domain, including the C-term helix-loop-helix, and the leucine zipper); no TFE3-PSF reciprocal transcript, as the der(X) t(X;1) is missing; the normal TFE3 transcript is found |
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| Entity | inv(X)(p11.2q12) in renal cell carcinoma --> NonO/TFE3 |
| Disease | only one case of papillary renal cell carcinoma |
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| Hybrid/Mutated Gene | 5' NONO- 3' TFE3 |
| Abnormal Protein | N-term NONO and most of it except the C-term proline rich sequence fused to the DNA binding domains of TFE3 (excluding the acidic transcriptional activation domain, including the C-term helix-loop-helix, and the leucine zipper); the reciprocal transcript is found |
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| Entity | Alveolar soft part sarcoma with ASPSCR1 -TFE3 fusion |
| Cytogenetics | der(X)t(X;17)(p11;q25) is consistently involved; it implicates: 1- the formation of a hybrid gene at the breakpoint, and also, 2- gain in Xp11-pter sequences, and loss of heterozygocity in 11q25-qter, with possible implications |
| Hybrid/Mutated Gene | 5' ASPSCR1-3' TFE3; the reciprocal 5' TFE3 - 3' ASPSCR1 is most often absent. ASPSCR1 is fused in frame to TFE3 exon 3 or 4 |
| Abnormal Protein | NH2 term ASPSCR1, fused to the C term of TFE3 |
| Oncogenesis | might combine the effect of a fusion protein to that of gene(s) dosage |
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| Entity | primary renal ASPSCR1-TFE3 tumour |
| Disease | a subset of renal cell carcinoma, which presents with a combination of alveolar soft part sarcoma-like features and epithelial features is found to carry this anomaly |
| Cytogenetics | balanced t(X;17)(p11.2;q25), in contrast with what is found in the alveolar soft part sarcoma (see above) |
| Hybrid/Mutated Gene | 5' ASPSCR1-3' TFE3 |
| Abnormal Protein | NH2 term ASPSCR1, fused to the C term of TFE3 |
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| Entity | other Xp11 involvements in renal cell carcinoma (t(X;10)(p11;q23), etc ...) are likely to implicate TFE3 |
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| TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. |
| Beckmann H, Su LK, Kadesch T |
| Genes & development. 1990 ; 4 (2) : 167-179. |
| PMID 2338243 |
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| The leucine zipper of TFE3 dictates helix-loop-helix dimerization specificity. |
| Beckmann H, Kadesch T |
| Genes & development. 1991 ; 5 (6) : 1057-1066. |
| PMID 2044953 |
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| A dominant negative form of transcription activator mTFE3 created by differential splicing. |
| Roman C, Cohn L, Calame K |
| Science (New York, N.Y.). 1991 ; 254 (5028) : 94-97. |
| PMID 1840705 |
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| Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas. |
| Weterman MA, Wilbrink M, Geurts van Kessel A |
| Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (26) : 15294-15298. |
| PMID 8986805 |
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| The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. |
| Sidhar SK, Clark J, Gill S, Hamoudi R, Crew AJ, Gwilliam R, Ross M, Linehan WM, Birdsall S, Shipley J, Cooper CS |
| Human molecular genetics. 1996 ; 5 (9) : 1333-1338. |
| PMID 8872474 |
| |
| Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma. |
| Clark J, Lu YJ, Sidhar SK, Parker C, Gill S, Smedley D, Hamoudi R, Linehan WM, Shipley J, Cooper CS |
| Oncogene. 1997 ; 15 (18) : 2233-2239. |
| PMID 9393982 |
| |
| The absence of the transcription activator TFE3 impairs activation of B cells in vivo. |
| Merrell K, Wells S, Henderson A, Gorman J, Alt F, Stall A, Calame K |
| Molecular and cellular biology. 1997 ; 17 (6) : 3335-3344. |
| PMID 9154832 |
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| Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins. |
| Weterman MJ, van Groningen JJ, Jansen A, van Kessel AG |
| Oncogene. 2000 ; 19 (1) : 69-74. |
| PMID 10644981 |
| |
| The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. |
| Ladanyi M, Lui MY, Antonescu CR, Krause-Boehm A, Meindl A, Argani P, Healey JH, Ueda T, Yoshikawa H, Meloni-Ehrig A, Sorensen PH, Mertens F, Mandahl N, van den Berghe H, Sciot R, Cin PD, Bridge J |
| Oncogene. 2001 ; 20 (1) : 48-57. |
| PMID 11244503 |
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| Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. |
| Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, Newbury R, Reuter VE, Garvin AJ, Perez-Atayde AR, Fletcher JA, Beckwith JB, Bridge JA, Ladanyi M |
| The American journal of pathology. 2001 ; 159 (1) : 179-192. |
| PMID 11438465 |
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| Transformation capacities of the papillary renal cell carcinoma-associated PRCCTFE3 and TFE3PRCC fusion genes. |
| Weterman MA, van Groningen JJ, den Hartog A, Geurts van Kessel A |
| Oncogene. 2001 ; 20 (12) : 1414-1424. |
| PMID 11313885 |
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| Fusion of a novel gene, RCC17, to the TFE3 gene in t(X;17)(p11.2;q25.3)-bearing papillary renal cell carcinomas. |
| Heimann P, El Housni H, Ogur G, Weterman MA, Petty EM, Vassart G |
| Cancer research. 2001 ; 61 (10) : 4130-4135. |
| PMID 11358836 |
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