hMLH1 promoter methylation and JC virus T antigen presence in the tumor tissue of colorectal cancer Israeli patients of different ethnic groups.
BACKGROUND
Hypermethylation of tumor suppressor genes' promoter and JC virus infection may be etiologic factors in the development of colorectal cancer (CRC).


OBJECTIVE
To look at both JC virus T antigen and hMLH1 promoter methylation in CRC tissue in Israeli ethnic groups with different incidence of CRC.


METHODS
Twenty-four consecutive patients with sporadic CRC were included in the study. Genomic DNA was isolated from paraffin-embedded microdomains removed from five slides of 7 mum by deparaffinizing in multiple xylene washes. Isolated DNA was used as a template for PCR to amplify DNA sequences coding the amino terminus of JC virus T antigen. Methylation-specific PCR was performed on bisulfite-modified DNA templates from CRC tissue materials to study methylation status of hMLH1 promoter, using two sets of primers specific for amplification of methylated and unmethylated alleles.


RESULTS
hMLH1 promoter methylation was observed in five patients (20.8%) who were also positive for JC virus T antigen, with even distribution among the ethnic groups. JC virus T antigen DNA was found in cancer tissues of 20 of the 24 patients; 50, 90.9, and 100% of Asia-Africa-born Jews, Europe-America-born Jews, and Israeli Arabs, respectively (P = 0.036 between the first group to the other).


CONCLUSIONS
Evidence for higher JC virus infection was shown among Europe-America-born Jews and Israeli Arabs. hMLH1 promoter methylation was evenly distributed between different ethnic groups in Israel.
Department of Gastroenterology, Rabin Medical Center, Beilinson Hospital, and Tel Aviv University, Israel. yniv@clalit.org.il
Yaron
Y
Niv
Alex
A
Vilkin
Baruch
B
Brenner
Yulia
Y
Kendel
Sara
S
Morgenstern
Zohar
Z
Levi
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000302:isolation & purification*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D015994:Incidence; D007557:Israel / Q000453:epidemiology; D007577:JC Virus / Q000302:isolation & purification*; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic
D048868:Adaptor Proteins, Signal Transducing; D000957:Antigens, Viral, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1