Diagnosis and management of a recurrent polymerase-epsilon (POLE)-mutated endometrial cancer

Veneris, Jennifer; Lee, Elizabeth K.; Goebel, Emily A.; Nucci, Marisa R.; Lindeman, Neal I.; Horowitz, Neil S.; Lee, Larissa; Raut, Chandrajit P.; Crotzer, David R.; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.; Campos, Susana M.

doi:10.1016/j.ygyno.2019.03.247

Cited by 23 publications

(18 citation statements)

References 37 publications

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“…Previous results suggest that POLE mutational status was associated with tumor mutational burden in endometrial cancers [32] consistent with our finding (Fig. 1c).…”

Section: Resultssupporting

confidence: 93%

“…Somatic mutations in POLE have been found in endometrial cancers in many studies. These reports include family studies that have confirmed the existence of novel POLE pathogenic germline variants and phenotypes of POLE-mutations in endometrial cancer (mutation analysis, clinical and lifestyle data, prognosis) [7, 32, 41, 42]. However, how do POLE mutations affect the prognosis of endometrial cancer?…”

Section: Discussionmentioning

confidence: 99%

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POLE mutations improve the prognosis of endometrial cancer via regulating cellular metabolism through AMF/AMFR signal transduction

Bian

Wang

et al. 2019

BMC Med Genet

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BackgroundThe morbidity and mortality of endometrial tumors, a common type of malignant cancer in women, have increased in recent years. POLE encodes the DNA polymerase ε, which is responsible for the leading strand DNA replication. Somatic mutations of POLE have been acknowledged in numerous cancers, resulting in the accumulation of DNA errors, leading to ultra-mutated tumors. Mutations in the exonuclease domain of POLE have been reported to improve progression-free survival in endometrial cancer. However, the potential relationship and underlying mechanism between POLE mutations and the prognosis of endometrial cancer patients remains unclear.MethodsThe whole exome sequencing data, RNA sequencing data, and clinical information were obtained from the TCGA database and employed for the analyses in this study. The detailed mutational information was analyzed using whole exome sequencing data and the mutated genes were shown with OncoPlot. The survival curves and cox proportional hazards regression analysis were used to accessed patient prognosis, the association of clinical characteristics and prognosis. Differentially expressed genes were analyzed by the edgeR R/Bioconductor package, then the GSEA Pre-ranked tool was used for Gene Set Enrichment Analysis (GSEA) to estimate the function of genes. Expression values were clustered using hierarchical clustering with Euclidean distance and ward linkage by the dendextend R package.ResultsPOLE mutational status was proven to be an independent prognostic factor for endometrial cancer patients. Patients with somatic POLE mutations presented a favorable prognosis. POLE mutations regulated glycolysis and cytokine secretion, affecting cell metabolism and immune response. Autocrine motility factor (AMF)/PGI and AMFR/gp78 exhibited higher expression levels in POLE mutant patients. The comprehensive high expressions of AMFR/gp78 and low expression of POLE were associated with the favorable prognosis of endometrial cancer patients.ConclusionsThis study showed the POLE mutations a vital factor in endometrial cancer patients, leading to a higher expression of AMF/PGI and AMFR/gp78. These results suggested comprehensive consideration of the POLE mutations, expression of AMF/PGI and AMFR/gp78 may provide a more feasible and effective approach for the treatment of endometrial cancer, which might improve the prognosis.

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“…Previous results suggest that POLE mutational status was associated with tumor mutational burden in endometrial cancers [32] consistent with our finding (Fig. 1c).…”

Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

POLE mutations improve the prognosis of endometrial cancer via regulating cellular metabolism through AMF/AMFR signal transduction

Bian

Wang

et al. 2019

BMC Med Genet

View full text Add to dashboard Cite

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“…Additionally, the amino acid changes underlying POLE mutations differed between the left‐ and right‐side colon. Currently, increasing research is focused on finding new markers for immunotherapy, and POLE gene mutations are considered a promising marker in various cancer types 18–20 . We advocate that more clinical trials should be focused on detecting POLE gene mutations to identify additional clinical features.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, increasing research is focused on finding new markers for immunotherapy, and POLE gene mutations are considered a promising marker in various cancer types. [18][19][20] We advocate that more clinical trials should be focused on detecting POLE gene mutations to identify additional clinical features. Here, we present an overview of the clinical patterns of patients with POLE mutations and report significant differences among diverse groups, which could contribute to identifying specific groups of patients who could benefit from immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Ultra‐mutated colorectal cancer patients withPOLEdriver mutations exhibit distinct clinical patterns

Cui

et al. 2020

Cancer Medicine

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“…The search strategy retrieved 72 articles. Overall, 18 reviews (21-38) and 8 case reports (39)(40)(41)(42)(43)(44)(45)(46) were identified, while 40 studies were deemed irrelevant. After removal of ineligible studies, 6 studies were recruited (47)(48)(49)(50)(51)(52).…”

Section: Data On Efficacy and Safetymentioning

confidence: 99%

Pembrolizumab in endometrial cancer: Where we stand now (Review)

et al. 2021

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Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms 'endometrial cancer' and 'pembrolizumab'. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice. Contents 1. Introduction 2. Sources and study selection 3. Data on efficacy and safety 4. Discussion 5. Conclusion

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Diagnosis and management of a recurrent polymerase-epsilon (POLE)-mutated endometrial cancer

Cited by 23 publications

References 37 publications

POLE mutations improve the prognosis of endometrial cancer via regulating cellular metabolism through AMF/AMFR signal transduction

POLE mutations improve the prognosis of endometrial cancer via regulating cellular metabolism through AMF/AMFR signal transduction

Ultra‐mutated colorectal cancer patients withPOLEdriver mutations exhibit distinct clinical patterns

Pembrolizumab in endometrial cancer: Where we stand now (Review)

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