Translocation Renal Cell Carcinomas: An Evolving Entity and a Member of the Microphthalmia Transcription Factor-Associated Family of Tumors

Bambury, Richard; Battley, Jodie E.; McCarthy, Andréa; Brady, Claire; O’Reilly, Seamus; Kelly, Paul; O'Brien, Frank; Sweeney, Paul; Fleming, Stewart; Mayer, Nick; Power, Derek G.

doi:10.1016/j.clgc.2012.12.006

Cited by 4 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During a mean follow-up of approximately 3 years, all patients were alive without evidence of disease. This experience is consistent with the limited existing literature 20,22 which has suggested favorable outcomes with partial nephrectomy in select patients with small translocation tumors.…”

Section: Discussionsupporting

confidence: 91%

Partial Nephrectomy for the Treatment of Translocation Renal Cell Carcinoma

Gorin

Ball

Pierorazio

et al. 2015

Clinical Genitourinary Cancer

View full text Add to dashboard Cite

We describe our experience with partial nephrectomy for the treatment of translocation renal cell carcinoma (RCC). During a 10-year period, 4 patients (0.02% of total RCC cases and 40% of translocation tumors) presented with an incidentally detected translocation RCC and were treated with partial nephrectomy. During a mean follow-up of 37 months, all patients were alive without evidence of disease. These data suggest that partial nephrectomy is a safe treatment option for select cases of translocation RCC. Background The aim of this study was to evaluate the outcome of patients with translocation renal cell carcinoma (RCC) treated with partial nephrectomy. Patients and Methods Our institutional review board-approved renal mass registry was queried for patients who underwent partial nephrectomy for a pathologically confirmed translocation RCC. We describe the demographic, clinical, pathological, and follow-up data for this series of patients. Results Between 2003 and 2013, 1897 patients with RCC were treated at our institution with a radical or partial nephrectomy. In total, 10 (0.5%) patients were diagnosed with a translocation RCC. Of these patients, 4 (40%) underwent treatment with partial nephrectomy for an incidentally detected small renal mass (mean imaging diameter, 2.6 cm [range, 1.0–4.2 cm]). During a mean follow-up of 37 months (range, 8–81 months), all patients were alive without evidence of disease. Conclusion At short-term follow-up, partial nephrectomy appears to be an effective treatment option for patients with small translocation RCCs. Larger studies are required to more extensively investigate the optimal treatment of these potentially aggressive tumors.

show abstract

Section: Discussionsupporting

confidence: 91%

Partial Nephrectomy for the Treatment of Translocation Renal Cell Carcinoma

Gorin

Ball

Pierorazio

et al. 2015

Clinical Genitourinary Cancer

View full text Add to dashboard Cite

show abstract

“…and has been subject to greater investigation than TFEB ‐tRCC. While seven fusion partners of TFE3 have been identified, almost all the 60 cases harboring TFEB structural rearrangements have presented fusions with a unique gene, MALAT1/Alpha located at 11q12 . The fusion gene conserves the complete TFEB coding sequence.…”

Section: Discussionmentioning

confidence: 99%

“…While seven fusion partners of TFE3 have been identified, [33][34][35][36][37][38][39] almost all the 60 cases harboring TFEB structural rearrangements have presented fusions with a unique gene, MALAT1/Alpha located at 11q12. 9,10,12,14,16,22,28,[30][31][32][33][42][43][44][45][46][47][48][49][50][51][52] The fusion gene conserves the complete TFEB coding sequence. Most breakpoints occur in a 289-bp breakpoint cluster region (BCR) upstream of TFEB exon 3 and in a 1,205-bp BCR within MALAT1.…”

Section: Casementioning

confidence: 99%

Comprehensive study of three novel cases of TFEB‐amplified renal cell carcinoma and review of the literature: Evidence for a specific entity with poor outcome

Mendel

Ambrosetti

Bodokh

et al. 2017

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

The first case of TFEB-amplified renal cell carcinoma was published in 2014. Since then, 29 additional cases have been described. The prognostic and therapeutic implications of this rare entity remain to be determined. We describe here the clinical, histological, and genetic features of three novel cases, and the first complete literature review. Four tumors were examined from three patients selected from the large collection of genetically characterized renal tumors in our institution. The pathological and immunohistochemical features were centrally reviewed by a uropathologist. Quantitative and structural genomic abnormalities were analyzed using comparative genomic hybridization, fluorescence in situ hybridization, and next generation sequencing. The three cases showed high-level amplification but no translocation of TFEB. Histologically, two tumors showed a papillary or pseudopapillary architecture. They did not show similarities with renal cell carcinoma harboring translocation of TFEB. The tumors were locally advanced high-grade lesions. They exhibited a metastatic course, which was rapidly leading to death in one patient. A second patient developed metastatic disease that did not respond to four lines of targeted treatments. The third patient had a protracted history of pulmonary and cardiac metastases. Complete clinical and biological data were examined and compared to those of the reported cases. Within the classification of renal tumors, TFEB-amplified renal cell carcinoma may constitute a novel entity characterized histologically by high-grade, papillary or pseudopapillary architecture, and necrotic remodeling and clinically by a poor outcome. Its pathogenesis has to be further characterized to develop appropriate targeted therapy.

show abstract

“…As an example, the microphthalmia-associated transcription factor (MITF), which acts by binding to E-box motifs and contains a DNA-binding basic helix–loop–helix leucine zipper (bHLH-Zip) as well as a dimerization motif, which allows homo- or heterodimerization with members of the “Mi” transcription family ( 7 ), has a main role in the pathogenesis of multiple tumor types. “Mi” transcription family members, such as TFE3 and TFEB, participate in the pathogenesis of a subgroup of renal cell carcinomas ( 8, 9 ), whereas MITF is key in melanocyte development ( 7, 10, 11 ) and also contributes to melanoma. In melanoma, MITF behaves as an oncogene when amplified ( 12 ) and facilitates melanoma invasiveness ( 13, 14 ) and therapy resistance ( 15, 16 ) when MITF levels are low.…”

Section: Introductionmentioning

confidence: 99%

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer

Santasusagna,

Zhu,

Jawalagatti

et al. 2023

Cancer Discovery

View full text Add to dashboard Cite

Signaling rewiring allows tumors survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer (PCa) unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprograming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5’-UTRs. Indeed, translation of the androgen receptor (AR) and major histocompatibility complex I (MHC-I) through this motif are sensitive to eIF3B amount. Notably, pharmacological targeting of eIF3B-dependent translation in pre-clinical models sensitizes PCa to ADT and anti-PD-1 therapy. These findings uncover a hidden connection between transcriptional and translational rewiring promoting therapy refractory lethal PCa and provide a druggable mechanism that may transcend into effective combined therapeutic strategies.

show abstract

Translocation Renal Cell Carcinomas: An Evolving Entity and a Member of the Microphthalmia Transcription Factor-Associated Family of Tumors

Cited by 4 publications

References 16 publications

Partial Nephrectomy for the Treatment of Translocation Renal Cell Carcinoma

Partial Nephrectomy for the Treatment of Translocation Renal Cell Carcinoma

Comprehensive study of three novel cases of TFEB‐amplified renal cell carcinoma and review of the literature: Evidence for a specific entity with poor outcome

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer

Contact Info

Product

Resources

About