2020
DOI: 10.1080/23723556.2020.1777060
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Molecular hallmarks of renal medullary carcinoma: more to c-MYC than meets the eye

Abstract: Renal medullary carcinoma (RMC) is a lethal disease that predominantly afflicts young individuals with sickle cell trait. Our recently reported molecular profiling of primary untreated RMC tissues elucidated distinct genomic and immune hallmarks of RMC, and identified MYC-induced replication stress as a targetable vulnerability for this disease.

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Cited by 12 publications
(14 citation statements)
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“…RMC is highly aggressive with most patients presenting metastatic disease at the time of diagnosis and less than 5% survive longer than 36 months (Carugo et al, 2019;Msaouel et al, 2020a). In addition, RMC tumours are resistant to targeted therapies used for other renal cancers and the best available cytotoxic chemotherapy regimens produce a brief objective response in less than 30% of cases (Msaouel et al, 2020b;Swartz et al, 2002). Alternative treatments such as antiangiogenics, EZH2 inhibitors and immunotherapy have been tested with varying success (Msaouel et al, 2020a).…”
Section: Introductionmentioning
confidence: 99%
“…RMC is highly aggressive with most patients presenting metastatic disease at the time of diagnosis and less than 5% survive longer than 36 months (Carugo et al, 2019;Msaouel et al, 2020a). In addition, RMC tumours are resistant to targeted therapies used for other renal cancers and the best available cytotoxic chemotherapy regimens produce a brief objective response in less than 30% of cases (Msaouel et al, 2020b;Swartz et al, 2002). Alternative treatments such as antiangiogenics, EZH2 inhibitors and immunotherapy have been tested with varying success (Msaouel et al, 2020a).…”
Section: Introductionmentioning
confidence: 99%
“…Likewise, bulk transcriptome data and in-vitro cell line experiments also support the increase in c-MYC activity and DNA repair stress following SMARCB1 inactivation in both RMC (13) (21) and MRT (37). The authors of the latter study concluded that a genetically-intact CDKN2A-p53 pathway is necessary for regulating the UPR pathway to buffer transformed cells against dramatic elevation of proteotoxic stress that results from activation of c-MYC (37).…”
Section: Discussionmentioning
confidence: 84%
“…We have mapped transcriptional signals from differentially expressed genes that are characteristic of RMC (13) (21) to distinct sub-populations of transformed renal epithelial cells originating from the TAL. We therefore tentatively put forward the TAL as a putative site-of-origin for RMC.…”
Section: Discussionmentioning
confidence: 99%
“…Our study is the first to suggest that increased renal hypoxia due to high-intensity exercise is a risk factor for RMC. While prior studies have evaluated the clinical characteristics, molecular landscape, and treatment outcomes of RMC, there is little evidence regarding potential modifiable risk factors for RMC [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. The exact mechanism linking renal medullary hypoxia to tumorigenesis, and loss of the SMARCB1 tumor suppressor in particular, remains to be determined.…”
Section: Discussionmentioning
confidence: 99%