MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights
Abstract
:1. Introduction
2. Clinical Entities
3. Pathological Features of TFE-tRCC
4. Molecular Features
4.1. Molecular Tool for tRCC Diagnosis
4.2. Partners of Fusion with TFE3
4.3. Additional Comprehensive Molecular Features of TFE3-tRCC
4.4. Transcriptomic Signatures of TFE3-tRCC
4.5. Molecular Features of TFEB-tRCC
5. Response to Modern Systemic Therapies
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ccRCC [21,22] | TFE3 RCC [3,7,13] | TFEB RCC [4,7,13] | |
---|---|---|---|
Incidence | Up to 75% of all RCCs | 1–4% of all adult RCCs Up to 40% of pediatric RCCs | <0.1% of all adult RCCs |
Mean age, years | 64 | 40 | 34 |
Sex ratio F–M | 2:1 | 1.6:1 | 0.75:1 |
Stage at diagnosis Metastatic | 1/3 of patients | 1/3 of patients Adults: 23–50% nodes involvement, mainly grade III. | Unknown |
Outcomes Median OS (stage IV) 5-years OS rate | 24 months 76% Stage I: 93%, II/III: 72%, IV: 12% | 18 months (adults) 86.6% (localized) Favorable up to 16 years old. Aggressive in adult patients | Unknown Unknown |
Risk factors | Age, sex, smoking, obesity, alcohol, hypertension, genetic predisposition (mainly Von Hippel–Lindau disease), trichloroethylene exposure | Prior chemotherapy | Unknown |
RCC Subtypes | TFE3 | Cathepsin K | HMB45 | Melan-A | CAIX | CK7 | AMACR |
---|---|---|---|---|---|---|---|
Xp11 tRCC | + | +/− | −/f+ | f+/− | −/f+ | − | + |
t(6;11) RCC | − | + | +/− | + | −/f+ | − | + |
Clear cell RCC | − | − | − | − | + | −/f+ | +low/− |
Papillary RCC | − | − | − | − | − | + | + |
Epithelioid angiomyolipoma | + | + | + | + | − | − | − |
Gene Fusion | Chromosome Translocation | Reference |
---|---|---|
ARID1B-TFE3 | t(X;6)(p11.2;q25) | [35] |
ASPSCR1-TFE3 | t(X;17)(p11.2;q25) | [36] |
CLTC-TFE3 | t(X;17)(p11.2;q23) | [33] |
DVL2-TFE3 | t(X;17)(p11.2;p13.1) | [31] |
FUBP1-TFE3 | t(X;1)(p11.2;p31.1) | [17] |
GRIPAP1-TFE3 | inv(X)(p11.23;p11.23) | [37] |
KAT6B-TFE3 | t(X;10)(p11.2;q22.2) | [38] |
KHSRP-TFE3 | t(X;19)(p11.2;p13) | [30] |
LUC7L3-TFE3 | t(X;17)(p11.2;q21) | [30] |
MATR3-TFE3 | T(X;5)(p11.2;q31.2) | [17] |
MED15-TFE3 | t(X;22)(p11.2;q11.2) | [17] |
NEAT1-TFE3 | t(X;11)(p11.2;q13.1) | [38] |
NonO-TFE3 | inv(X)(p11.2;q13) | [32] |
PARP14-TFE3 | t(X;3)(p11.2;q23) | [39] |
PRCC-TFE3 | t(X;1)(p11.2;q21) | [40] |
RBM10-TFE3 | Inv(X)(p11.2;p11.23) | [34] |
RBMX-TFE3 | Inv(X)(p11;q26) | [41] |
SETD1B-TFE3 | t(X;12)(p11.2;q24.31) | [42] |
SFPQ-TFE3 | t(X;1)(p11.2;p34) | [43] |
ZC3H4-TFE3 | t(X;19)(p11.2;q13.32) | [44] |
Ref. | Type of Study | Line of Treatment | Number of Patients | Treatment | Response | Survival Outcomes |
---|---|---|---|---|---|---|
[50] | Retrospective | 1.2 | 15 (Xp11.2, adults) | VEGF-targeted therapy (sunitinib, sorafenib, bevacizumab) | PR 3/15 SD 7/15 PD 5/15 | PFS = 7.1 mon OS = 14.3 mon |
[51] | Retrospective | 1 | 20 (Xp11.2, adults, youth) | Sunitinib, cytokines | Sunitinib: CR 1/11 PR 3/11 SD 6/11 PD 1/11 Cytokines: PR 1/9 SD 2/9 PD 6/9 | PFS Sunitinib: 8.2 mon Cytokines: 2 mon OS Sunitinib: not reached Cytokines: 17 mon |
[51] | Retrospective | ≥2 | 17 (Xp11.2 adults, youth) | Sunitinib, sorafenib, mTOR inhibitor | Sunitinib: PR 3/3 Sorafenib: SD 7/8 mTOR: PR 1/7, SD 6/7 | PFS Sunitinib: 11 mon Sorafenib: 9 mon mTOR: 3 mon |
[52] | Retrospective | ≥2 | 24 | anti-PD1, anti-CTLA4, anti-PD1–anti-CTLA4 | CR 0 PR 4/24 SD 3/24 | PFS = 2.5 mon OS = 24 mon |
[53] | Prospective phase 2 | ≥1 | 60 (various histology,5 tRCC) | Atezolizumab +bevacizumab | ORR 20% SD 80% (tRCC) | Not reported for tRCC cohort. |
[54] | Retrospective | ≥1 | 24 | Cabozantinib | CR 4% ORR = 17% DCR (ORR + SD) 62.5% | PFS = 8.4 mon OS = 17 mon |
Trials | Clinical Phase | Population | Number of Patients | Treatment | Primary Endpoint | Status * |
---|---|---|---|---|---|---|
KEYNOTE-B61 NCT04704219 | 2 | nccRCC | 152 | Pembrolizumab +Lenvatinib (single arm) | ORR | Not yet recruiting |
NCT03541902 | 2 | nccRCC | 84 | Cabozantinib vs. sunitinib | PFS | Recruiting |
NCT03685448 | 2 | nccRCC | 48 | Cabozantinib (single arm) | ORR | Recruiting |
NCT03595124 | 2 | tRCC | 40 | Axitinib +nivolumab vs. Nivolumab or Axitinib | PFS | Recruiting |
NCT04413123 | 2 | nccRCC | 60 | Cabozantinib +nivolumab +ipilimumab | ORR | Recruiting |
NCT03635892 | 2 | nccRCC | 97 | Nivolumab +cabozantinib (single arm) | ORR | Recruiting |
UNISoN NCT03177239/ ANZUP 1602 | 2 | nccRCC | 85 | Nivolumab +ipilimumab (single arm) | ORR | Active, not recruiting |
NCT03075423/ SUNNIFORECAST | 2 | nccRCC | 306 | Nivolumab +ipilimumab vs. sunitinib | OS rate at 12 mon | Recruiting |
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Simonaggio, A.; Ambrosetti, D.; Verkarre, V.; Auvray, M.; Oudard, S.; Vano, Y.-A. MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights. Int. J. Mol. Sci. 2022, 23, 7649. https://doi.org/10.3390/ijms23147649
Simonaggio A, Ambrosetti D, Verkarre V, Auvray M, Oudard S, Vano Y-A. MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights. International Journal of Molecular Sciences. 2022; 23(14):7649. https://doi.org/10.3390/ijms23147649
Chicago/Turabian StyleSimonaggio, Audrey, Damien Ambrosetti, Virginie Verkarre, Marie Auvray, Stéphane Oudard, and Yann-Alexandre Vano. 2022. "MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights" International Journal of Molecular Sciences 23, no. 14: 7649. https://doi.org/10.3390/ijms23147649