Low frequency of epigenetic events in urothelial tumors in young patients

Helen C. Owen, J. Giedl, Peter J. Wild, Samson W. Fine, Peter A. Humphrey, Louis P. Dehner, Mahul Amin, Johnathan I. Epstein, H. Blaszyk, David Hughes, Arndt Hartmann, Robert Stoehr, James W. Catto

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Abstract

Purpose: Bladder urothelial cell carcinoma is uncommon in young patients. We recently reported a series of tumors in patients younger than 20 years at diagnosis and performed exhaustive genetic screening for molecular alterations. Few events typical of bladder urothelial cell carcinoma were detected. Since many carcinogenic events occur at the epigenetic rather than the genetic level, we analyzed the same tumors for alterations in DNA hypermethylation. We compared our findings with those in tumors in older patients with similar pathological profiles. Materials and Methods: We analyzed 76 bladder urothelial cell carcinomas from 3 groups stratified by age at diagnosis, including less than 19, 20 to 45 and greater than 46 years (median 78), and matched for low grade and nonmuscle invasive stage. We used quantified methyl specific polymerase chain reaction to investigate promoter methylation for 8 tumor suppressor genes implicated in urothelial carcinogenesis. Results: Tumors in the youngest age group had the lowest incidence of global hypermethylation compared to the other tumors with a methyl index of 37.5% vs 62.5% and 50%, respectively (ANOVA p = 0.009). When individual loci were analyzed, younger patients had a significantly lower rate and concentration of methylation at APC, Bcl2, MGMT and E-cadherin promoters than in the older groups (p <0.05). Few differences were present between the 2 older cohorts but the APC and MGMT methylation concentration increased with age. Conclusions: Urothelial tumors in patients younger than 19 years have a low rate of epigenetic alteration. Tumors in patients older than 20 years have epigenetic profiles similar to those of tumors in patients within the typical bladder urothelial cell carcinoma age range.

Original languageEnglish (US)
Pages (from-to)459-463
Number of pages5
JournalJournal of Urology
Volume184
Issue number2
DOIs
StatePublished - Jun 17 2010

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Epigenomics
Neoplasms
Urinary Bladder
Methylation
Carcinoma
Age Groups
Genetic Testing
Cadherins
Tumor Suppressor Genes
Analysis of Variance
Carcinogenesis
Polymerase Chain Reaction
DNA
Incidence

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Owen, H. C., Giedl, J., Wild, P. J., Fine, S. W., Humphrey, P. A., Dehner, L. P., ... Catto, J. W. (2010). Low frequency of epigenetic events in urothelial tumors in young patients. Journal of Urology, 184(2), 459-463. https://doi.org/10.1016/j.juro.2010.03.131

Low frequency of epigenetic events in urothelial tumors in young patients. / Owen, Helen C.; Giedl, J.; Wild, Peter J.; Fine, Samson W.; Humphrey, Peter A.; Dehner, Louis P.; Amin, Mahul; Epstein, Johnathan I.; Blaszyk, H.; Hughes, David; Hartmann, Arndt; Stoehr, Robert; Catto, James W.

In: Journal of Urology, Vol. 184, No. 2, 17.06.2010, p. 459-463.

Research output: Contribution to journalArticle

Owen, HC, Giedl, J, Wild, PJ, Fine, SW, Humphrey, PA, Dehner, LP, Amin, M, Epstein, JI, Blaszyk, H, Hughes, D, Hartmann, A, Stoehr, R & Catto, JW 2010, 'Low frequency of epigenetic events in urothelial tumors in young patients', Journal of Urology, vol. 184, no. 2, pp. 459-463. https://doi.org/10.1016/j.juro.2010.03.131
Owen HC, Giedl J, Wild PJ, Fine SW, Humphrey PA, Dehner LP et al. Low frequency of epigenetic events in urothelial tumors in young patients. Journal of Urology. 2010 Jun 17;184(2):459-463. https://doi.org/10.1016/j.juro.2010.03.131
Owen, Helen C. ; Giedl, J. ; Wild, Peter J. ; Fine, Samson W. ; Humphrey, Peter A. ; Dehner, Louis P. ; Amin, Mahul ; Epstein, Johnathan I. ; Blaszyk, H. ; Hughes, David ; Hartmann, Arndt ; Stoehr, Robert ; Catto, James W. / Low frequency of epigenetic events in urothelial tumors in young patients. In: Journal of Urology. 2010 ; Vol. 184, No. 2. pp. 459-463.
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abstract = "Purpose: Bladder urothelial cell carcinoma is uncommon in young patients. We recently reported a series of tumors in patients younger than 20 years at diagnosis and performed exhaustive genetic screening for molecular alterations. Few events typical of bladder urothelial cell carcinoma were detected. Since many carcinogenic events occur at the epigenetic rather than the genetic level, we analyzed the same tumors for alterations in DNA hypermethylation. We compared our findings with those in tumors in older patients with similar pathological profiles. Materials and Methods: We analyzed 76 bladder urothelial cell carcinomas from 3 groups stratified by age at diagnosis, including less than 19, 20 to 45 and greater than 46 years (median 78), and matched for low grade and nonmuscle invasive stage. We used quantified methyl specific polymerase chain reaction to investigate promoter methylation for 8 tumor suppressor genes implicated in urothelial carcinogenesis. Results: Tumors in the youngest age group had the lowest incidence of global hypermethylation compared to the other tumors with a methyl index of 37.5{\%} vs 62.5{\%} and 50{\%}, respectively (ANOVA p = 0.009). When individual loci were analyzed, younger patients had a significantly lower rate and concentration of methylation at APC, Bcl2, MGMT and E-cadherin promoters than in the older groups (p <0.05). Few differences were present between the 2 older cohorts but the APC and MGMT methylation concentration increased with age. Conclusions: Urothelial tumors in patients younger than 19 years have a low rate of epigenetic alteration. Tumors in patients older than 20 years have epigenetic profiles similar to those of tumors in patients within the typical bladder urothelial cell carcinoma age range.",
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AU - Giedl, J.

AU - Wild, Peter J.

AU - Fine, Samson W.

AU - Humphrey, Peter A.

AU - Dehner, Louis P.

AU - Amin, Mahul

AU - Epstein, Johnathan I.

AU - Blaszyk, H.

AU - Hughes, David

AU - Hartmann, Arndt

AU - Stoehr, Robert

AU - Catto, James W.

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N2 - Purpose: Bladder urothelial cell carcinoma is uncommon in young patients. We recently reported a series of tumors in patients younger than 20 years at diagnosis and performed exhaustive genetic screening for molecular alterations. Few events typical of bladder urothelial cell carcinoma were detected. Since many carcinogenic events occur at the epigenetic rather than the genetic level, we analyzed the same tumors for alterations in DNA hypermethylation. We compared our findings with those in tumors in older patients with similar pathological profiles. Materials and Methods: We analyzed 76 bladder urothelial cell carcinomas from 3 groups stratified by age at diagnosis, including less than 19, 20 to 45 and greater than 46 years (median 78), and matched for low grade and nonmuscle invasive stage. We used quantified methyl specific polymerase chain reaction to investigate promoter methylation for 8 tumor suppressor genes implicated in urothelial carcinogenesis. Results: Tumors in the youngest age group had the lowest incidence of global hypermethylation compared to the other tumors with a methyl index of 37.5% vs 62.5% and 50%, respectively (ANOVA p = 0.009). When individual loci were analyzed, younger patients had a significantly lower rate and concentration of methylation at APC, Bcl2, MGMT and E-cadherin promoters than in the older groups (p <0.05). Few differences were present between the 2 older cohorts but the APC and MGMT methylation concentration increased with age. Conclusions: Urothelial tumors in patients younger than 19 years have a low rate of epigenetic alteration. Tumors in patients older than 20 years have epigenetic profiles similar to those of tumors in patients within the typical bladder urothelial cell carcinoma age range.

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