DNA Methylation and Urological Cancer, a Step Towards Personalized Medicine: Current and Future Prospects
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REVIEW ARTICLE
DNA Methylation and Urological Cancer, a Step Towards Personalized Medicine: Current and Future Prospects Javier C. Angulo1 • Jose I. Lo´pez2 • Santiago Ropero3
Ó Springer International Publishing Switzerland 2016
Abstract Urologic malignancies are some of the commonest tumors often curable when diagnosed at early stage. However, accurate diagnostic markers and faithful predictors of prognosis are needed to avoid over-diagnosis leading to overtreatment. Many promising exploratory studies have identified epigenetic markers in urinary malignancies based on DNA methylation, histone modification and non-coding ribonucleic acid (ncRNA) expression that epigenetically regulate gene expression. We review and discuss the current state of development and the future potential of epigenetic biomarkers for more accurate and less invasive detection of urological cancer, tumor recurrence and progression of disease serving to establish diagnosis and monitor treatment efficacies. The specific clinical implications of such methylation tests on therapeutic decisions and patient outcome and current limitations are also discussed.
& Javier C. Angulo [email protected] 1
Servicio de Urologı´a, Hospital Universitario de Getafe, Departamento Clı´nico, Facultad de Ciencias Biome´dicas, Universidad Europea de Madrid, Laureate Universities, Hospital Universitario de Getafe, Carretera de Toledo Km 12.5, Getafe, 28905 Madrid, Spain
2
Servicio de Anatomı´a Patolo´gica, Hospital Universitario de Cruces, Instituto BioCruces,Universidad del Paı´s Vasco (UPV-EHU), Bilbao, Spain
3
Departamento de Biologı´a de Sistemas, Unidad Docente de Bioquı´mica y Biologı´a Molecular, Universidad de Alcala´, Alcala´ de Henares, Madrid, Spain
Key Points for Decision Makers Epigenetic alterations (DNA aberrant methylation, histone-modification, long non-coding RNAs and microRNAs) are common in urologic neoplasia and have great potential for future use as biomarkers. Some microRNAs and gene methylation patterns allow establishment of cancer-specific signatures with diagnostic implications, and also for the evaluation of prognosis and the prediction of response to certain therapies. Detection of cell-free DNA hypermethylation at various gene sites is specific for patients with urologic cancer, but generally speaking diagnostic accuracy is limited by moderate sensitivity. Multigene analysis may increase the sensitivity of a particular assay. Different neoplasias share hypermethylation profiles in part and this overlapping may decrease organ specificity. Epigenetic phenomena associated with aging and environmental factors may interfere with the accuracy of epigenetic based biomarkers of tumor development and progression. Epigenetic treatment may reprogram the pattern of gene expression in cancer cells.
1 Introduction Genitourinary cancers comprise a heterogeneous class of malignancies with a very high prevalence worldwide and are associated with significant morbidity and mortality.
J. C. Angulo et al.
Among them, prostate adenocarcinoma is
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