title: Presence of JC virus DNA in the tumor tissue and normal mucosa of patients with sporadic colorectal cancer (CRC) or with positive family history and Bethesda criteria.
abstract: BACKGROUND
  JC virus (JCV) may infect the gastrointestinal tract in childhood, and, by encoding a gene for T-antigen (T Ag), can initiate chromosomal instability in epithelial cells.
  
  
  OBJECTIVE
  We looked for JCV DNA in the cancer tissue of patients with sporadic colorectal cancer (CRC, Group A) and with positive family history and Bethesda criteria (Group B). We hypothesized that the role of JCV may be different between these two groups.
  
  
  METHODS
  Fifty-six patients were randomly selected from our database, 30 in Group A and 26 in Group B. DNA was isolated from the tumor, normal mucosa, and plasma, and JCV DNA sequences were looked for with specific polymerase chain reaction (PCR) assays for T Ag primers. Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed on paraffin-embedded tissue.
  
  
  RESULTS
  In Group A, T Ag was demonstrated in 6 (20.00%) and 3 (10.00%) of the tumors and adjacent normal mucosa, respectively (P = 0.094). In Group B, the corresponding observations were 10 (38.46%) and 6 (23.07%), respectively (P < 0.001). Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed in all of the Group A and B patients. All patients of Group A (100%) showed expression of these proteins, while only 19 patients of Group B did so (73.1%), P = 0.009. JCV T Ag DNA was found in 20, 28.5, and 42.1% of the tumors in Group A, Group B with negative staining for DNA repair genes, and Group B with a positive staining, respectively (NS).
  
  
  CONCLUSIONS
  CRC patients with positive family history have a higher incidence of JCV T Ag, but this did not correlate with specific DNA repair gene mutations. We could not conclude that, on the background of genetic mutation in one of the DNA repair genes, JCV acts as the missing link in the chain of events leading to CRC.
authors.affiliation: Department of Gastroenterology and Pathology, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Alex
authors.initials: A
authors.lastname: Vilkin
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ronen
authors.forename: Zohar
authors.initials: Z
authors.lastname: Levi
authors.forename: Sara
authors.initials: S
authors.lastname: Morgenstern
authors.forename: Marisa
authors.initials: M
authors.lastname: Halpern
authors.forename: Yaron
authors.initials: Y
authors.lastname: Niv
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D043171:Chromosomal Instability / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D045643:DNA Repair Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D007577:JC Virus / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000957:Antigens, Viral, Tumor; D004273:DNA, Neoplasm; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes