JC virus and colorectal cancer: a possible trigger in the chromosomal instability pathways.
OBJECTIVE
Most colorectal cancers (CRCs) have deletions, duplications, and rearrangements of their chromosomes that reflect a destabilizing process called chromosomal instability (CIN). The cause of CIN is controversial, but no intrinsic mutation in cancer cells has been reported that can reasonably account for this in CRC. This review explores the new hypothesis that JC virus (JCV) may be the cause of CIN.


RESULTS
A polyomavirus has been found in most colon cancers that encodes a T-antigen gene, which can induce CIN in several laboratory models. This virus, JCV, infects virtually every human population that has been investigated, and evidence for the virus has been found in the gastrointestinal tracts of most healthy adults. It is hypothesized that the virus infects the gut in childhood and remains there in a latent form for most people. In people who develop colorectal neoplasia, it is proposed that the virus is activated, and expression of the oncogene-T-antigen-leads to CIN. This form of genomic instability is necessary to explain the losses of tumor suppressor genes that occur in the context of the multistep carcinogenesis pathway. Furthermore, it is proposed that once neoplastic colonic epithelial cells have experienced biallelic inactivation of a critical number of tissue-specific tumor suppressor genes-including APC and p53-the ongoing effect of the transforming virus may be relatively deleterious to a neoplastic cell, and selective pressure may lead to loss of viral infection.


CONCLUSIONS
This review summarizes the experimental data that have led to the hypothesis that JCV is a common cause of CIN in CRC.
Niv
Yaron
Y
Department of Gastroenterology, Rabin Medical Center, Beilinson Campus, Tel Aviv University, Israel. yniv@clalit.org.il
Goel
Ajay
A
Boland
C Richard
CR
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000821:virology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D041981:Gastrointestinal Tract / Q000821:virology; D006801:Humans; D007577:JC Virus / Q000276:immunology / Q000472:pathogenicity*; D015534:Trans-Activators / Q000502:physiology; D051176:beta Catenin
D000914:Antibodies, Viral; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin