CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder cancer

Marina I. Gutiérrez, Abdul K. Siraj, Hussein Khaled, Natalie Koon, Wael El-Rifai, Kishor Bhatia

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Urothelial carcinomas (TCC) constitute the vast majority of bladder cancers in most of the world. On the other hand, squamous cell bladder carcinoma, a rare subtype in the Western world, is a common subtype in areas with endemic Schistosoma infection. Although schistosomal infection has been reported to influence DNA methylation, the pattern and extent of CpG island hypermethylation in squamous cell carcinomas remain unknown. In this study, we used methylation-specific PCR to characterize 12 cancer-related genes in 41 bladder cancer samples from Egypt (31 squamous cell carcinomas (SCC), 21 of them associated with Schistosoma and 10 TCC, five of which were Schistosoma- associated). The genes analyzed included E-cadherin, DAP-Kinase, O 6MGMT, p14, p15, p16, FHIT, APC, RASSF1A, GSTP1, RARβ and p73. Methylation of at least one gene was detected in all squamous cell tumors except two, and 45% of samples had at least three methylated genes. The average methylation index was 0.24, corresponding to three of the 12 analyzed genes. Schistosoma-associated tumors had more genes methylated than non-Schistosoma tumors (average MI: 0.29 vs 0.14) (P = 0.027). Although the extent of methylation in TCC (average MI: 0.16) was lower than in squamous cell carcinomas (SCC), the overall profile of methylation was similar, with Schistosoma-associated cases having a higher methylation index. Our results suggest that schistosomal involvement associates with a greater degree of epigenetic changes in the bladder epithelium.

Original languageEnglish (US)
Pages (from-to)1268-1274
Number of pages7
JournalModern Pathology
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Schistosoma
CpG Islands
Urinary Bladder Neoplasms
Methylation
Squamous Cell Carcinoma
Genes
Urinary Bladder
Death-Associated Protein Kinases
Neoplasms
Western World
Egypt
Neoplasm Genes
DNA Methylation
Cadherins
Infection
Epigenomics
Epithelium
Epithelial Cells
Carcinoma
Polymerase Chain Reaction

Keywords

  • Bilharziasis
  • Concurrent hypermethylation
  • Epigenetics
  • Infection
  • Methylator phenotype
  • Squamous cell carcinoma
  • Transitional cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder cancer. / Gutiérrez, Marina I.; Siraj, Abdul K.; Khaled, Hussein; Koon, Natalie; El-Rifai, Wael; Bhatia, Kishor.

In: Modern Pathology, Vol. 17, No. 10, 01.10.2004, p. 1268-1274.

Research output: Contribution to journalArticle

Gutiérrez, Marina I. ; Siraj, Abdul K. ; Khaled, Hussein ; Koon, Natalie ; El-Rifai, Wael ; Bhatia, Kishor. / CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder cancer. In: Modern Pathology. 2004 ; Vol. 17, No. 10. pp. 1268-1274.
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AU - Khaled, Hussein

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AB - Urothelial carcinomas (TCC) constitute the vast majority of bladder cancers in most of the world. On the other hand, squamous cell bladder carcinoma, a rare subtype in the Western world, is a common subtype in areas with endemic Schistosoma infection. Although schistosomal infection has been reported to influence DNA methylation, the pattern and extent of CpG island hypermethylation in squamous cell carcinomas remain unknown. In this study, we used methylation-specific PCR to characterize 12 cancer-related genes in 41 bladder cancer samples from Egypt (31 squamous cell carcinomas (SCC), 21 of them associated with Schistosoma and 10 TCC, five of which were Schistosoma- associated). The genes analyzed included E-cadherin, DAP-Kinase, O 6MGMT, p14, p15, p16, FHIT, APC, RASSF1A, GSTP1, RARβ and p73. Methylation of at least one gene was detected in all squamous cell tumors except two, and 45% of samples had at least three methylated genes. The average methylation index was 0.24, corresponding to three of the 12 analyzed genes. Schistosoma-associated tumors had more genes methylated than non-Schistosoma tumors (average MI: 0.29 vs 0.14) (P = 0.027). Although the extent of methylation in TCC (average MI: 0.16) was lower than in squamous cell carcinomas (SCC), the overall profile of methylation was similar, with Schistosoma-associated cases having a higher methylation index. Our results suggest that schistosomal involvement associates with a greater degree of epigenetic changes in the bladder epithelium.

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KW - Methylator phenotype

KW - Squamous cell carcinoma

KW - Transitional cell carcinoma

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