SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts

Blattner, Mirjam; Lee, Dong Hoon; O’Reilly, Catherine; Park, Kyung; MacDonald, Theresa Y.; Khani, Francesca; Turner, Kimberly L.; Chiu, Ya Lin; Wild, Peter J.; Dolgalev, Igor; Heguy, Adriana; Sboner, Andrea; Ramazangolu, Sinan; Hieronymus, Haley; Sawyers, Charles L.; Tewari, Ashutosh; Moch, Holger; Yoon, Ghil Suk; Known, Yong Chul; Andrén, Ove; Fall, Katja; Demichelis, F.; Mosquera, Juan Miguel; Robinson, Brian D.; Barbieri, Christopher E.; Rubin, Mark A.

doi:10.1593/neo.131704

Cited by 135 publications

(149 citation statements)

References 26 publications

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“…According to these findings, the status of T2E has also been taken into account for our prognosis analyses finding a strong association between SPOP expression and prognosis in the group of patients not harbouring the translocation. In our series, the mutational analysis has been performed in this subgroup of patients finding a mutation rate of 10%, which is in line with previous studies [5,17]. Some of these mutations have been previously described in other works [5,[17][18][19][20][21], however this is the first time that mutations p.F104V, p.D153N and p.Q120Stop were reported.…”

Section: Discussionsupporting

confidence: 90%

“…In our series, the mutational analysis has been performed in this subgroup of patients finding a mutation rate of 10%, which is in line with previous studies [5,17]. Some of these mutations have been previously described in other works [5,[17][18][19][20][21], however this is the first time that mutations p.F104V, p.D153N and p.Q120Stop were reported. Furthermore, the association between SPOP mutations and expression was studied and despite no statistical significance was found all the mutated cases showed a down-regulation of SPOP.…”

Section: Discussionsupporting

confidence: 90%

“…Association between SPOP mutations, clinicopathological characteristics and patient outcome has only been evaluated in a multi-institutional study where no significant association was found [17]. Nevertheless, our study shows for the first time that the presence of mutations in SPOP leads to a worse prognosis; hence, selecting patients with time to biochemical progression lower (median time 19 months) compared with those with no SPOP mutations (median time 69 months).…”

Section: Discussionmentioning

confidence: 67%

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Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer

García-Flores

Casanova-Salas

Rubio‐Briones

et al. 2014

European Journal of Cancer

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer

García-Flores

Casanova-Salas

Rubio‐Briones

et al. 2014

European Journal of Cancer

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“…Like ERG translocation events, genetic alterations of the SPOPencoding gene are also connected to prostate cancer (193). Most of SPOP mutations are concentrated in the MATH domain (for example, Y87C and F133V mutations), which is crucial for substrate recognition (194).…”

Section: Degradation Impaired Through Decreased E3 Ligase Activitymentioning

confidence: 99%

“…Consequently, mutations that inactivate SPOP function are present in 15% of prostate cancers (193). Increased SPOP is associated with other forms of cancer, most notably ccRCC.…”

Section: Tumorigenesis: Somewhere Between Neutrality and Lethalitymentioning

confidence: 99%

Degrons in cancer

et al. 2017

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Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the cell cycle and monitoring cellular hypoxia. Degrons enable the elimination of proteins that are no longer required, preventing their possible dysfunction. Although the human genome encodes~600 E3 ubiquitin ligases, only a fraction of these enzymes have well-defined target degrons. Thus, for most cellular proteins, the destruction mechanisms are poorly understood. This is important for many diseases, especially for cancer, a disease that involves the enhanced expression of oncogenes and the persistence of encoded oncoproteins coupled with reduced abundance of tumor suppressors. Lossof-function mutations occur in the degrons of several oncoproteins, such as the transcription factors MYC and NRF2, and in various mitogenic receptors, such as NOTCH1 and several receptor tyrosine kinases. Mutations eliminating the function of the b-catenin degron are found in many cancers and are considered one of the most abundant mutations driving carcinogenesis. In this Review, we describe the current knowledge of degrons in cancer and suggest that increased research on the "dark degrome" (unknown degron-E3 relationships) would enhance progress in cancer research.

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Determination of TMPRSS2‐ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis

Ovalle

Sanabria‐Salas

Mesa

et al. 2023

Cell Biology International

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Prostate cancer (PCa) is one of cancer with of the highest incidence and mortality worldwide. Current disease prognostic markers do not differentiate aggressive from indolent PCa with sufficient certainty, and characterization by molecular subtypes has been sought to allow a better classification. TMPRSS2‐ERG, SPOP, FOXA1, and IDH1 molecular subtypes have been described, but the association of these subtypes with prognosis in PCa is unclear; their frequency in Colombian patients is also unknown. Formalin‐fixed and paraffin‐embedded samples of radical prostatectomy from 112 patients with PCa were used. The TMPRSS2‐ERG subtype was assessed with fluorescent in situ hybridization. The mutations in SPOP, FOXA1, and IDH1 in hot‐spot regions were evaluated using Sanger sequencing. Fusion was detected in 71 patients (63.4%). No statistically significant differences were found between the state of fusion and the variables analyzed. In the 41 fusion‐negative cases (36.6%), two patients (4.9%) had missense mutations in SPOP (p.F102C and p.F133L), representing a 1.8% of the overall cohort. The low frequency of this subtype in Colombians could be explained by the reported variability in the frequency of these mutations according to the population (5%–20%). No mutations were found in FOXA1 in the cases analyzed. The synonym SNP rs11554137 IDH1105GGT was found in tumor tissue but not in the normal tissue in one case. A larger cohort of Colombian PCa patients is needed for future studies to validate these findings and gain a better understanding of the molecular profile of this cancer in our population and if there are any differences by Colombian regions.

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SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts

Cited by 135 publications

References 26 publications

Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer

Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer

Degrons in cancer

Determination of TMPRSS2‐ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis

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