TFE3 translocation

Upregulation of GSTP1 mediated by chimeric TFE3 promotes TFE3-tRCC progression by targeting JNK signaling pathway, which underscore the potential of GSTP1 as a promising therapeutic target for TFE3-tRCC.

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.