2016-08-01   Pedram Argani  

1.Department of Pathology, The Johns Hopkins Hospital, Baltimore MD (PA) pargani@jhmi.edu

Summary

Atlas Image
t(X;1)(p11;q21) (G banding) - Courtesy Francois Desangles.

Abstract

Review on Renal cell carcinoma with t(X;1)(p11;q21) PRCC/TFE3, with data on clinics, and the genes involve

Classification

Classification

Xp11 translocation renal cell carcinoma (RCCs) harbor gene fusions involving TFE3 transcription factor. The The t(6;11) RCCs harbor a specific MALAT1 (Alpha) - TFEB gene fusion. TFEB and TFE3 belong to the same MiT subfamily of transcription factors. Because of similarities at the clinical, morphologic, immunohistochemical, and genetic levels, the Xp11 translocation RCCs and t(6;11) RCCs are currently grouped together under the category of MiT family translocation renal cell carcinoma.)

Clinics and Pathology

Phenotype stem cell origin

t(X;1) (p11;q21) PRCC/TFE3 is found in Xp11 translocation renal cell carcinoma.

Epidemiology

Approximately 40 reported cases, median age 20 yrs (range 2-69); sex ratio: 17M/20F. A subset of cases has been associated with prior exposure to cytotoxic chemotherapy.

Pathology

PRCC frequently have papillary architecture with clear cytoplasm and abundant psammoma bodies. Other cases are nested and mimic clear cell RCC.

Treatment

Radical nephrectomy.

Prognosis

Similar to that of others papillary renal cell carcinoma.

Cytogenetics

Probes

TFE3 and PRCC/TFE3

Additional anomalies

+17.

Genes Involved and Proteins

Gene name

TFE3 (transcription factor E3)

Location

Xp11.23

Protein description

Transcription factor; binds to the immunoglobulin enhancer.

Gene name

PRCC (papillary renal cell carcinoma)

Location

1q23.1

Protein description

491aa; widely expressed; proline rich.

Result of the chromosomal anomaly

Description

5 TFE3 - 3 PRCC and 5 PRCC - 3 TFE3

Detection protocole

positional cloning; screening in a tumor cDNA library and hybridization with TFE3

Description

PRCC/TFE3 fusion protein includes the transcription activating, helix-loop-helix and leucine-zipper domains of TFE3; the TFE3/PRCC fusion protein (513 amino acids) is also expressed.

Highly cited references

Pubmed IDYearTitleCitations
127665782003Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay.117
250488602014Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers.101
129176402003A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23).73
88724741996The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene.71
192287222009Adult Xp11 translocation renal cell carcinoma diagnosed by cytogenetics and immunohistochemistry.66
124596222002PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21).60
269750362016TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers.50
165750032006Translocation carcinomas of the kidney after chemotherapy in childhood.47
243093272014Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage.46
193961492009Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas.36
216028172011Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions.35
153163112004Morphologic and molecular characterization of renal cell carcinoma in children and young adults.34
310061672019MicroRNA-204-5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma.20
232887012013Combining integrated genomics and functional genomics to dissect the biology of a cancer-associated, aberrant transcription factor, the ASPSCR1-TFE3 fusion oncoprotein.20
297130412018RNA sequencing of Xp11 translocation-associated cancers reveals novel gene fusions and distinctive clinicopathologic correlations.18
113139422001PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors.15
310434882019TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease.13
160105492005Renal cell carcinoma in a pediatric patient with an inherited mitochondrial mutation.10
123515852002Understanding familial and non-familial renal cell cancer.9
330198422021PRCC-TFE3 fusion-mediated PRKN/parkin-dependent mitophagy promotes cell survival and proliferation in PRCC-TFE3 translocation renal cell carcinoma.8
289499762017PRCC-TFE3 dual-fusion FISH assay: A new method for identifying PRCC-TFE3 renal cell carcinoma in paraffin-embedded tissue.7
232246032012A renal epithelioid angiomyolipoma/perivascular epithelioid cell tumor with TFE3 gene break visualized by FISH.6
335922662021The positive regulation loop between NRF1 and NONO-TFE3 fusion promotes phase separation and aggregation of NONO-TFE3 in NONO-TFE3 tRCC.5
314335282019Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors.5
314002302019Gene fusion analysis in renal cell carcinoma by FusionPlex RNA-sequencing and correlations of molecular findings with clinicopathological features.4
307879902019Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a micropapillary pattern: cases report and literature review.3
284156462017Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11 translocation RCC: comparison of three different diagnostic methods.3
195634132009Adult-onset renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion with smooth muscle stroma and abnormal vessels.3
303242432018Monensin induces cell death by autophagy and inhibits matrix metalloproteinase 7 (MMP7) in UOK146 renal cell carcinoma cell line.2
354521812022Both SUMOylation and ubiquitination of TFE3 fusion protein regulated by androgen receptor are the potential target in the therapy of Xp11.2 translocation renal cell carcinoma.1
353967732022Targeting chemoresistance in Xp11.2 translocation renal cell carcinoma using a novel polyamide-chlorambucil conjugate.1
323393582020PRCC-TFE3 regulates migration and invasion of translocation renal cell carcinomas via activation of Drp1-dependent mitochondrial fission.1
247169152014Asparagus racemosus leaf extract inhibits growth of UOK 146 renal cell carcinoma cell line: simultaneous oncogenic PRCCTFE3 fusion transcript inhibition and apoptosis independent cell death.1
351185872022Phenotypical screening on metastatic PRCC-TFE3 fusion translocation renal cell carcinoma organoids reveals potential therapeutic agents.0
349175112021Xp11.2 Translocation Renal Cell Carcinoma With TFE3 Rearrangement: Distinct Morphological Features and Prognosis With Different Fusion Partners.0
326769672021Ocular PEComas are frequently melanotic and TFE3-translocated: report of two cases including the first description of PRCC-TFE3 fusion in PEComa.0
214249372011Re-evaluation of histological type by immunohistochemical and genetic study of transcription factors (TFE3 and TFEB) of VHL gene mutation-negative clear cell renal cell carcinoma and other special types of renal tumor.0
210925832010[Clinicopathologic and molecular genetic study of renal cell carcinoma occurring in teenagers].0
168077662006PRCC-TFE3 renal cell carcinoma in a boy with a history of contralateral mesoblastic nephroma.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
91996391997Papillary (chromophil) renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases.Amin MB et al
124596222002PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21).Argani P et al
165750032006Translocation carcinomas of the kidney after chemotherapy in childhood.Argani P et al
67724441980Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA.Auffray C et al
85273831995Distinct Xp11.2 breakpoints in two renal cell carcinomas exhibiting X;autosome translocations.Dijkhuizen T et al
243093272014Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage.Ellis CL et al
84319101993Translocation (X;1) in papillary renal cell carcinoma. A new cytogenetic subtype.Meloni AM et al
16845321991Cytogenetics of a renal cell carcinoma in a 17-month-old child. Evidence for Xp11.2 as a recurring breakpoint.Tomlinson GE et al
89868051996Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas.Weterman MA et al
30046981986Cytogenetics of a renal adenocarcinoma in a 2-year-old child.de Jong B et al
91404591997Cytogenetic classification of renal cell cancer.van den Berg E et al

Citation

Pedram Argani

Atlas Genet Cytogenet Oncol Haematol. 2016-08-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/5009/tx1id5009

Historical Card

1998-03-01 Kidney: Renal cell carcinoma with t(X;1)(p11;q21) PRCC/TFE3 by  François Desangles