Association of JC virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers.
OBJECTIVE
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.
Goel
Ajay
A
Division of Gastroenterology, Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas 75246, USA.
Li
Mei-Shu
MS
Nagasaka
Takeshi
T
Shin
Sung Kwan
SK
Fuerst
Florentine
F
Ricciardiello
Luigi
L
Wasserman
Linda
L
Boland
C Richard
CR
D000704:Analysis of Variance; D000957:Antigens, Viral, Tumor / Q000032:analysis / Q000378:metabolism*; D001483:Base Sequence; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019175:DNA Methylation; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics* / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011336:Probability; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D014412:Tumor Virus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology
D000957:Antigens, Viral, Tumor; D014408:Biomarkers, Tumor; D004279:DNA, Viral