Generic placeholder image

Current Genomics


ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Opinion Article

DNA Methylation and Bladder Cancer: Where Genotype does not Predict Phenotype

Author(s): Amit Sharma, Heiko Reutter and Jörg Ellinger*

Volume 21, Issue 1, 2020

Page: [34 - 36] Pages: 3

DOI: 10.2174/1389202921666200102163422

Price: $65


Nearly three decades ago, the association between Bladder cancer (BC) and DNA methylation has initially been reported. Indeed, in the recent years, the mechanism connecting these two has gained deeper insights. Still, the mediocre performance of DNA methylation markers in the clinics raises the major concern. Strikingly, whether it is the inter-individual methylation variations or the paucity of knowledge about methylation fingerprints lying within histologically distinct subtypes of BC requires critical discussion. In the future, besides identifying the initial causative factors, it will be important to illustrate the cascade of events that determines the fraction of the genome to convey altered methylation patterns specific towards each cancer type.

Keywords: Bladder cancer, DNA methylation, epigenetic, cancer biomarkers, genotype, phenotype.

Graphical Abstract
Antoni, S.; Ferlay, J.; Soerjomataram, I.; Znaor, A.; Jemal, A.; Bray, F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur. Urol., 2017, 71(1), 96-108.
[] [PMID: 27370177]
Burger, M.; Catto, J.W.; Dalbagni, G.; Grossman, H.B.; Herr, H.; Karakiewicz, P.; Kassouf, W.; Kiemeney, L.A.; La Vecchia, C.; Shariat, S.; Lotan, Y. Epidemiology and risk factors of urothelial bladder cancer. Eur. Urol., 2013, 63(2), 234-241.
[] [PMID: 22877502]
Del Senno, L.; Maestri, I.; Piva, R.; Hanau, S.; Reggiani, A.; Romano, A.; Russo, G. Differential hypomethylation of the c-myc protooncogene in bladder cancers at different stages and grades. J. Urol., 1989, 142(1), 146-149.
[] [PMID: 2733094]
Bender, C.M.; Pao, M.M.; Jones, P.A. Inhibition of DNA methylation by 5-aza-2′-deoxycytidine suppresses the growth of human tumor cell lines. Cancer Res., 1998, 58(1), 95-101.
[PMID: 9426064]
Chan, M.W.; Chan, L.W.; Tang, N.L.; Tong, J.H.; Lo, K.W.; Lee, T.L.; Cheung, H.Y.; Wong, W.S.; Chan, P.S.; Lai, F.M.; To, K.F. Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Clin. Cancer Res., 2002, 8(2), 464-470.
[PMID: 11839665]
Chihara, Y.; Kanai, Y.; Fujimoto, H.; Sugano, K.; Kawashima, K.; Liang, G.; Jones, P.A.; Fujimoto, K.; Kuniyasu, H.; Hirao, Y. Diagnostic markers of urothelial cancer based on DNA methylation analysis. BMC Cancer, 2013, 13, 275.
[] [PMID: 23735005]
Hartana, C.A.; Ahlén Bergman, E.; Broomé, A.; Berglund, S.; Johansson, M.; Alamdari, F.; Jakubczyk, T.; Huge, Y.; Aljabery, F.; Palmqvist, K.; Holmström, B.; Glise, H.; Riklund, K.; Sherif, A.; Winqvist, O. Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer. Clin. Exp. Immunol., 2018, 194(1), 39-53.
[] [PMID: 30009527]
Zhao, R.; Choi, B.Y.; Lee, M.H.; Bode, A.M.; Dong, Z. Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer. EBioMedicine, 2016, 8, 30-39.
[] [PMID: 27428416]
Chuang, J.C.; Warner, S.L.; Vollmer, D.; Vankayalapati, H.; Redkar, S.; Bearss, D.J.; Qiu, X.; Yoo, C.B.; Jones, P.A. S110, a 5-Aza-2′-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol. Cancer Ther., 2010, 9(5), 1443-1450.
[] [PMID: 20442312]
Hynds, R.E.; Vladimirou, E.; Janes, S.M. The secret lives of cancer cell lines. Dis. Model. Mech., 2018, 11(11)037366
[] [PMID: 30459183]
Sharma, A.; Stei, M.M.; Fröhlich, H.; Holz, F.G.; Loeffler, K.U.; Herwig-Carl, M.C. Genetic and epigenetic insights into uveal melanoma. Clin. Genet., 2018, 93(5), 952-961.
[] [PMID: 28902406]
Sharma, A.; Fröhlich, H.; Zhang, R.; Ebert, A.K.; Rösch, W.; Reis, H.; Kristiansen, G.; Ellinger, J.; Reutter, H. Classic bladder exstrophy and adenocarcinoma of the bladder: Methylome analysis provide no evidence for underlying disease-mechanisms of this association. Cancer Genet., 2019, 235-236, 18-20.
[] [PMID: 31296310]
Jordahl, K.M.; Randolph, T.W.; Song, X.; Sather, C.L.; Tinker, L.F.; Phipps, A.I.; Kelsey, K.T.; White, E.; Bhatti, P. Genome-wide DNA methylation in prediagnostic blood and bladder cancer risk in the women’s health initiative. Cancer Epidemiol. Biomarkers Prev., 2018, 27(6), 689-695.
[] [PMID: 29540343]
van der Heijden, A.G.; Mengual, L.; Ingelmo-Torres, M.; Lozano, J.J.; van Rijt-van de Westerlo, C.C.M.; Baixauli, M.; Geavlete, B.; Moldoveanud, C.; Ene, C.; Dinney, C.P.; Czerniak, B.; Schalken, J.A.; Kiemeney, L.A.L.M.; Ribal, M.J.; Witjes, J.A.; Alcaraz, A. urine cell-based DNA methylation classifier for monitoring bladder cancer. Clin. Epigenetics, 2018, 10, 71.
[] [PMID: 29854012]
Sharma, A.; Biswas, A.; Liu, H.; Sen, S.; Paruchuri, A.; Katsonis, P.; Lichtarge, O.; Chand Dakal, T.; Maulik, U.; Gromiha, M.M.; Bandyopadhyay, S.; Ludwig, M.; Holz, F.G.; Loeffler, K.U.; Herwig-Carl, M.C. Mutational landscape of the BAP1 locus reveals an intrinsic control to regulate the miRNA network and the binding of protein complexes in uveal melanoma. Cancers (Basel), 2019, 11(10)E1600
[] [PMID: 31635116]
Sharma, A.; Osato, N.; Liu, H.; Asthana, S.; Dakal, T.C.; Ambrosini, G.; Bucher, P.; Schmitt, I.; Wüllner, U. Common genetic variants associated with Parkinson’s disease display widespread signature of epigenetic plasticity. Sci. Rep., 2019, 9(1), 18464.
[] [PMID: 31804560]
Casadevall, D.; Kilian, A.Y.; Bellmunt, J. The prognostic role of epigenetic dysregulation in bladder cancer: a systematic review. Cancer Treat. Rev., 2017, 61, 82-93.
[] [PMID: 29121502]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy