Association of JC Virus T-Antigen Expression With the Methylator Phenotype in Sporadic Colorectal Cancers

Ajay Goel, Mei Shu Li, Takeshi Nagasaka, Sung Kwan Shin, Florentine Fuerst, Luigi Ricciardiello, Linda Wasserman, C. Richard Boland

Research output: Contribution to journalArticle

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Abstract

Background & Aims: JC virus (JCV) is a polyomavirus that ubiquitously infects humans and has been implicated in various human cancers. JCV encodes a "transforming" gene, T-antigen (T-Ag), which is believed to mediate the oncogenic potential of the virus. We have previously shown that JCV DNA sequences are usually present in human colorectal cancers (CRCs), and we have provided in vitro evidence that JCV can induce chromosomal instability (CIN) in CRC cells. This study tests the hypothesis that JCV T-Ag expression correlates with one or more forms of genomic or epigenetic instability in sporadic CRCs. Methods: We characterized 100 sporadic CRCs for microsatellite instability (MSI) and CIN. PCR amplifications were performed for T-Ag sequences, and immunohistochemical (IHC) staining was performed to detect T-Ag expression. De novo methylation of the promoter regions of nine putative tumor suppressor genes thought to play a role in colorectal carcinogenesis was studied by methylation-specific PCR. Results: JCV T-Ag DNA sequences were found in 77% of the CRCs and 56% of these cancers (or 43% of the total) expressed T-Ag by IHC. Significant associations were observed between T-Ag expression and CIN in CRCs (P = .017) and between T-Ag expression and promoter methylation of multiple genes (P = .01). Conclusions: The association between T-Ag expression and promoter methylation in CRC suggests that this viral oncogene may induce methylator phenotype and that JCV may be involved in CRC through multiple mechanisms of genetic and epigenetic instability.

Original languageEnglish
Pages (from-to)1950-1961
Number of pages12
JournalGastroenterology
Volume130
Issue number7
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

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JC Virus
Viral Tumor Antigens
Colorectal Neoplasms
Phenotype
Chromosomal Instability
Methylation
Oncogenes
Epigenomics
Polymerase Chain Reaction
Polyomavirus
Oncogenic Viruses
Microsatellite Instability
Tumor Suppressor Genes
Genetic Promoter Regions
Neoplasms
Carcinogenesis
Staining and Labeling

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Goel, A., Li, M. S., Nagasaka, T., Shin, S. K., Fuerst, F., Ricciardiello, L., ... Boland, C. R. (2006). Association of JC Virus T-Antigen Expression With the Methylator Phenotype in Sporadic Colorectal Cancers. Gastroenterology, 130(7), 1950-1961. https://doi.org/10.1053/j.gastro.2006.02.061

Association of JC Virus T-Antigen Expression With the Methylator Phenotype in Sporadic Colorectal Cancers. / Goel, Ajay; Li, Mei Shu; Nagasaka, Takeshi; Shin, Sung Kwan; Fuerst, Florentine; Ricciardiello, Luigi; Wasserman, Linda; Boland, C. Richard.

In: Gastroenterology, Vol. 130, No. 7, 07.2006, p. 1950-1961.

Research output: Contribution to journalArticle

Goel, A, Li, MS, Nagasaka, T, Shin, SK, Fuerst, F, Ricciardiello, L, Wasserman, L & Boland, CR 2006, 'Association of JC Virus T-Antigen Expression With the Methylator Phenotype in Sporadic Colorectal Cancers', Gastroenterology, vol. 130, no. 7, pp. 1950-1961. https://doi.org/10.1053/j.gastro.2006.02.061
Goel, Ajay ; Li, Mei Shu ; Nagasaka, Takeshi ; Shin, Sung Kwan ; Fuerst, Florentine ; Ricciardiello, Luigi ; Wasserman, Linda ; Boland, C. Richard. / Association of JC Virus T-Antigen Expression With the Methylator Phenotype in Sporadic Colorectal Cancers. In: Gastroenterology. 2006 ; Vol. 130, No. 7. pp. 1950-1961.
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