TFE3 translocation

Extra-renal RCC, a rare entity, occurs in locations outside the normal kidneys. This report presents a case of metastatic primary extra-renal RCC.

Finally, we applied our model to predict gene dependencies in tumors from the TCGA (11,373 tumors; 28 lineages) and multiple additional rare cancers (958 tumors across 16 types, including 13 distinct subtypes of kidney cancer), nominating potentially actionable vulnerabilities in several poorly-characterized cancer types. Our results couple unbiased functional genetic screening with a predictive model to establish a landscape of candidate vulnerabilities across cancers, including several rare cancers currently lacking in potential targets.

It is not well understood why similar gene fusions can give rise to renal tumors with different morpho-immunophenotypes, which may contribute to the recent disagreement regarding their classification. However, as these two entities, respectively, epithelial and mesenchymal in nature, are widely recognized by the pathology community and their clinicopathologic features well established, we overall believe it is still better to retain the names TFE3-rearranged renal cell carcinoma and TFE3-rearranged PEComa.

We clarified the patient's challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.

Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition. The concept of "non-hereditary" familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.

Furthermore, D-mannose treatment dramatically improves the therapeutic efficacy of MEK inhibitor (MEKi) trametinib in vivo. Our findings unveil a universally unrecognized anti-tumor mechanism of D-mannose by destabilizing PD-1 and provide strategies to enhance the efficacy of both immune checkpoint blockade (ICB) and MEKi -based therapies.

This study not only proposed a high-precision clinical prediction model composed of various variables for the early diagnosis of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma but also optimized therapeutic strategies through prognostic analysis.

For example, most MED15::TFE3 fusion associated RCCs exhibit multilocular cystic morphology, mimicking multilocular cystic renal neoplasm of low malignant potential. Here we present a case of MED15::TFE3 RCC in an older adult and review the literature with an emphasis on practical diagnostic approaches for predominantly cystic, low-grade, clear cell renal tumors.

The way in which the B-cells in ASPS may contribute to the exceptional responses seen with D-T may be related more to the pre-existing numbers of B-cells and independent of lymphoid aggregation. Further work in this area should focus on the mechanisms underlying this ASPS-specific intratumoral B-cell and to enhance presence of B-cells in other sarcoma types. Additional analyses on these trial samples are ongoing to further delineate the role B-cells in ASPS response to D-T.

AKR1B10+/2SC+/FH- cases can be diagnosed as FH-deficient RCC. Patients with AKR1B10+/2SC+/FH+ are highly suspicious for FH-deficient RCC and should be referred for FH genetic tests.

Clinical TFE3/TFEB FISH assays successfully identified and confirmed rare MiTF-RCC with TFE3 and TFEB rearrangements. Although morphologic and biomarker features associated with a kidney tumor may be suggestive of MiTF-RCC, clinical TFE3/TFEB FISH assays are crucial for a confirmation and definitive subclassification of patients with MiTF-RCC.

Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in children and adolescents are mostly large cystic and solid mixed echo masses, with high echo of solid components, and often accompanied by cystic changes and calcification. Its ultrasonic manifestations have certain characteristics. Color Doppler ultrasound has a certain diagnostic value for this disease.

Cytomorphologic and immunocytochemical features of TFE3 translocation-associated renal cell carcinoma.

To date, 12 of the 15 MED15::TFE3 fusion renal cell carcinomas published in the literature are cystic, with three being extensively cystic. Thus, if a multilocular cystic renal neoplasm is encountered in a kidney specimen, translocation renal cell carcinoma should be included in the differential diagnosis as cystic MED15::TFE3 tRCCs carry an uncertain prognosis making recognition for future characterization necessary.

The patient had metastatic disease and was treated by surgery and five lines of therapy, including 24 months of stable disease on the MET inhibitor cabozantinib, with an overall survival of 7?years. In addition to expanding the spectrum of TFE3 rearrangement partners, this report highlights the complexity of these tumors and supports the development of translational programs in renal cancer.

Xp11.2 RCC showed moderate enhancement during the renal corticomedullary phase and delayed enhancement during the nephrographic phase and excretory phase. Xp11.2 RCC has a higher incidence in children.

This case was a TFE3 translocation RCC with rare morphological features. Through this case report, we emphasize the importance of in situ detection of TFE3 gene translocation and protein in TFE3 translocation RCC.

TFE3 rearranged RCC has different molecular alterations compared to cRCC and pRCC. Despite it having a relatively cold TME compared to pRCC and ccRCC, increased PDL1+ rates in TFE3 translocation RCC suggest a potential benefit from immune checkpoint inhibitor therapy and warrants further investigation in this rare RCC subtype.

Clinical TFE3 / TFEB FISH assays successfully identified those rare MiTF-RCC with TFE3 and TFEB rearrangements. TFE3 and TFEB translocations tend to occur in relatively younger patients TFEB amplifications occur more frequently than TFEB translocations in renal tumors and manifest largely in older patients.

This study found that nuclear TFE3 expression is not specific to the Xp11.2 translocation RCC. Moreover, the positive TFE3 expression is associated with tumor progression and poor prognosis in patients with RCC irrespective of the presence of TFE3 translocation.

In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC.

TRAF3IP2 functions as an oncogene in NONO-TFE3 tRCC progression and might serve as a novel target for NONO-TFE3 tRCC therapy.

Xp11.2 translocation RCC is a type of renal cell carcinoma with a relatively low incidence and various prognoses. Early-stage Xp11.2 translocation RCCs have a similar prognosis to most typical RCCs, but late-stage Xp11.2 translocation RCCs can lead to poor oncological outcomes.

These tumors are likely a precursor to or represent an early event in the development of TFE3 translocation renal cell carcinomas. An understanding of such tumors to translocation renal cell carcinoma progression can provide insight into the pathogenic mechanism, and ultimately aid the diagnosis and management of translocation renal cell carcinoma.

No abstract available

Androgen and AR function as facilitators in Xp11.2 tRCC progression and may be a novel therapeutic target for Xp11.2 tRCC. The combined use of AR antagonist MDV3100 and UCHL1 inhibitor 6RK73 increased both the SUMOylation and ubiquitination of the PRCC-TFE3 fusion protein.

Herein we provided a comprehensive analysis of ∼400 tRCC cases with known TFE3 fusion partners, estimated their relative incidence and summarized clinicomorphologic features associated with most common fusion subtypes. Our data was based on an extensive literature review and had a special focus on comparing immunohistochemistry, fluorescent in situ hybridization and contemporary molecular studies for the accurate diagnosis of tRCC.

P2, N=48, Recruiting, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | Trial primary completion date: Apr 2022 --> Oct 2022

This type of kidney cancer was a rare subtype. Because of its complex and changeable shape, it has a high degree of overlap with other kidney cancer subtypes, and the missed diagnosis rate and misdiagnosis rate are extremely high. The diagnosis is mainly based on pathomorphology and immunohistochemistry, TFE3 positive expression and TFE3 gene destruction and rearrangement.

We identified a novel VCP-TFE3 fusion in Xp11.2 translocation RCCs for the first time, which has unique morphology and worse prognosis than those with other variant TFE3 rearrangements. Integration of morphological, immunohistochemical, and molecular methods is often necessary for the precise diagnosis and optimal clinical management of malignant tumors.

TFE3-rearranged EHE is a rare and novel molecular subtype of vascular tumors. Compared with classic EHE, TFE3-rearranged EHE showed a broad morphological spectrum, including well-formed vascular spaces, solid nests and sheets of eosinophilic or clear epithelioid cells, spindle cell components and absence of obvious myxohyaline stroma. Familiar with the clinicopathological spetrum of TFE3-rearranged EHE and increasing of immunohistochemistry and molecular detection of TFE3 in the diagnosis of vascular tumors, will be helpful to identify this new molecular subtype.

Our results indicate that E2 amplifies TOP2β-mediated TFE3 breaks by ERα-dependent pathway, and E2 upregulates TFE3 by NRF1 to increase the risk of TFE3 breaks. This suggests that E2 is an important pathogenic factor for Xp11.2 tRCC pathogenesis. Video Abstract.

In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with ASPSCR1-TFE3 fusion. Here, we describe the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.

In contrast, tuberous sclerosis complex-related neoplasms often enter the differential for tumors with eosinophilic cytology. This review provides an overview of the clinical, gross, microscopic, immunohistochemical, genetic, and molecular alterations in key renal neoplasms occurring more commonly in females; differential diagnoses are also discussed regardless of sex predilection.

The differential diagnosis for T2PRCC includes a variety of other renal tumors, including aggressive entities such as TFE3 translocation-associated renal cell carcinoma, TFEB-amplified renal cell carcinoma, fumarate hydratase-deficient renal cell carcinoma, high-grade CCRCC, and collecting duct carcinoma. Accurate classification of these tumors is important for prognostication and selection of therapy.

HIF-1α is a potential target for therapy of NONO-TFE3 tRCC under hypoxia.