Integrative clinical and molecular characterization of translocation renal cell carcinoma

Bakouny, Ziad; Sadagopan, Ananthan; Ravi, Praful; Metaferia, Nebiyou Y.; Li, Jiao; AbuHammad, Shatha; Tang, Stephen; Denize, Thomas; Garner, Emma R.; Gào, Xīn; Braun, David A.; Hirsch, Laure; Steinharter, John A.; Bouchard, Gabrielle; Walton, Emily; West, Destiny; Labaki, Chris; Dudani, Shaan; Gan, Chun-Loo; Sethunath, Vidyalakshmi; Carvalho, Filipe; Imamović, Alma; Ricker, Cora A.; Vokes, Natalie I.; Nyman, Jackson; Berchuck, Jacob E.; Park, Jihye; Hirsch, Michelle S.; Haq, Rizwan; Lee, Gwo‐Shu Mary; McGregor, Bradley A.; Chang, Steven L.; Feldman, Adam S.; Wu, Catherine J.; McDermott, David F.; Heng, Daniel Y.C.; Signoretti, Sabina; Allen, Eliezer M. Van; Choueiri, Toni K.; Viswanathan, Srinivas R.

doi:10.1016/j.celrep.2021.110190

Cited by 48 publications

(63 citation statements)

References 139 publications

(183 reference statements)

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“…Both TFE3 and TFEB tRCCs may overlap with each other’s and with other RCCs’ morphologies, in particular with clear cell RCC, papillary RCC or, more rarely, clear cell papillary renal cell carcinomas as well as perivascular epithelioid cell tumors (PEComas). These overlapped features may lead to the misclassification of tRCC if the specific immunohistochemistry required for diagnosis is missing, as observed, in particular, in TCGA RCC cohorts [ 7 ]. TFE3 tRCC diagnosis is proposed based on the analysis of both morphological and immunohistochemical features.…”

Section: Pathological Features Of Tfe-trccmentioning

confidence: 99%

“…Approximately 20 distinct partners have been described to date [ 10 , 20 ] ( Table 3 ). The most common partners involved in TFE3-tRCC are PRCC (papillary renal cell carcinoma) with t(X;1)(p11.2;q21.2), ASPSCR1 ( ASPL) (alveolar soft part sarcoma locus) with the t(X;17)(p11.2;q25) and SFPQ (splicing factor proline- and glutamine-rich protein) with t(X;1)(p11.2;p34) [ 7 , 20 , 31 ]. Less recurrent TFE3 fusion partners include NONO (non-POU domain containing octamer binding) resulting from inv(X) (p11.2q12) [ 32 ], CLTC (clathrin heavy chain) resulting from t(X; 17) (p11.2; q23) [ 33 ] and RBM10 (RNA binding motif protein 10) resulting from inv(X) (p11.2p11.23) [ 34 ].…”

Section: Molecular Featuresmentioning

confidence: 99%

“…Less recurrent TFE3 fusion partners include NONO (non-POU domain containing octamer binding) resulting from inv(X) (p11.2q12) [ 32 ], CLTC (clathrin heavy chain) resulting from t(X; 17) (p11.2; q23) [ 33 ] and RBM10 (RNA binding motif protein 10) resulting from inv(X) (p11.2p11.23) [ 34 ]. Despite great diversity breakpoints of TFE3, all fusions preserved the C-terminal helix–loop–helix/leucine zipper domain (HLH-LZ) of the MiT/TFE transcription factor, which is critical for dimerization and DNA binding, and thus activation [ 7 ].…”

Section: Molecular Featuresmentioning

confidence: 99%

“…The Xp11 RCCs (TFE3-tRCC) were first described in 1991 by Tomlinson et al in a 17-month-old child and considered as “juvenile RCC” [ 6 ]. TFE3-tRCC represents 89% of all tRCCs [ 7 ]. Although TFE3-tRCC predominantly affects children and young adults, it can also be encountered in older populations.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, TFE3 and TFEB were grouped together under the title “MITF/TFE translocation renal carcinoma” in the 2016 WHO classification [ 11 ] and then were separated into two distinct molecularly-defined entities in the recent WHO classification, 2022, as TFE3-rearranged RCC and TFEB-rearranged RCC [ 12 ]. Fusions involving MITF are very rare and have been identified in only 2% of cases [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights

Simonaggio

Verkarre

Kuentz

et al. 2022

IJMS

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MiTF/TFE translocation renal cell carcinoma (tRCC) is a rare and aggressive subtype of RCC representing the most prevalent RCC in the pediatric population (up to 40%) and making up 4% of all RCCs in adults. It is characterized by translocations involving either TFE3 (TFE3-tRCC), TFEB (TFEB-tRCC) or MITF, all members of the MIT family (microphthalmia-associated transcriptional factor). TFE3-tRCC was first recognized in the World Health Organization (WHO) classification of kidney cancers in 2004. In contrast to TFEB-tRCC, TFE3-tRCC is associated with many partners that can be detected by RNA or exome sequencing. Both diagnoses of TFE3 and TFEB-tRCC are performed on morphological and immunohistochemical features, but, to date, TFE break-apart fluorescent in situ hybridization (FISH) remains the gold standard for diagnosis. The clinical behavior of tRCC is heterogeneous and more aggressive in adults. Management of metastatic tRCC is challenging, especially in the younger population, and data are scarce. Efficacy of the standard of care-targeted therapies and immune checkpoint inhibitors remains low. Recent integrative exome and RNA sequencing analyses have provided a better understanding of the biological heterogeneity, which can contribute to a better therapeutic approach. We describe the clinico-pathological entities, the response to systemic therapy and the molecular features and techniques used to diagnose tRCC.

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Section: Pathological Features Of Tfe-trccmentioning

confidence: 99%

Section: Molecular Featuresmentioning

confidence: 99%

Section: Molecular Featuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights

Simonaggio

Verkarre

Kuentz

et al. 2022

IJMS

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ANGPTL2‐mediated epigenetic repression of MHC‐I in tumor cells accelerates tumor immune evasion

et al. 2023

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Loss or downregulation of major histocompatibility complex class I (MHC‐I) contributes to tumor immune evasion. We previously demonstrated that angiopoietin‐like protein 2 (ANGPTL2) promotes tumor progression using a Xp11.2 translocation renal cell carcinoma (tRCC) mouse model. However, molecular mechanisms underlying ANGPTL2 tumor‐promoting activity in the tRCC model remained unclear. Here, we report that ANGPTL2 deficiency in renal tubular epithelial cells slows tumor progression in the tRCC mouse model and promotes activated CD8+ T‐cell infiltration of kidney tissues. We also found that Angptl2‐deficient tumor cells show enhanced interferon γ‐induced expression of MHC‐I and increased susceptibility to CD8+ T‐cell‐mediated anti‐tumor immune responses. Moreover, we provide evidence that the ANGPTL2‐α5β1 integrin pathway accelerates polycomb repressive complex 2‐mediated repression of MHC‐I expression in tumor cells. These findings suggest that ANGPTL2 signaling in tumor cells contributes to tumor immune evasion and that suppressing that signaling in tumor cells could serve as a potential strategy to facilitate tumor elimination by T‐cell‐mediated anti‐tumor immunity.

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A novel VCP::TFE3 gene fusion resulting from t(X;9)(p11.23;p13.3) chromosome translocation in TFE3 rearranged renal cancer cell carcinoma

Kuentz

Gimenez-Roqueplo

Just

et al. 2023

Genes Chromosomes & Cancer

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Renal cell carcinoma (RCC) with rearrangement of transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3; TFE3-rearranged RCC) at Xp11.2 is a rare tumor entity but the most frequent among the microphthalmia transcription factor family translocation RCCs. Here, we report the identification of a new VCP::TFE3 fusion gene as the result of a t(X;9)(p11.23;p13.3) translocation identified by whole transcriptome sequencing. No other relevant molecular alteration was identified by whole exome sequencing. This case showed typical morphological features of TFE3rearranged RCC with positive TFE3 immunostaining and positive TFE3 break-apart fluorescence in situ hybridization. MET was also overexpressed on immunohistochemistry. The patient had metastatic disease and was treated by surgery and five lines of therapy, including 24 months of stable disease on the mesenchymal epithelial transition (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.

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Integrative clinical and molecular characterization of translocation renal cell carcinoma

Cited by 48 publications

References 139 publications

MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights

MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights

ANGPTL2‐mediated epigenetic repression of MHC‐I in tumor cells accelerates tumor immune evasion

A novel VCP::TFE3 gene fusion resulting from t(X;9)(p11.23;p13.3) chromosome translocation in TFE3 rearranged renal cancer cell carcinoma

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