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Background:Colorectal cancer (CRC) is the second most common cancer in the Kingdom of Saudi Arabia with ever increasing
incidence rates. DNA methylation is a common event in CRC where it is now considered an important phenomenon in CRC
carcinogenesis and useful for the classification and prognosis of CRC.
Methods:
To gain insight into the molecular mechanisms underpinning CRC in Saudi Arabian patients, the DNA methylation
frequency of key genes were profiled (MLH1, MSH2, RASSF1A, SLIT2, HIC1, MGMT, SFRP1, MYOD1, APC, CDKN2A, as
well as five CIMP markers) in 120 sporadic CRC cases. CRC tumors originating from the rectum, left, and right colons are
represented in this cohort of formalin-fixed paraffin-embedded tissues.
Results:
The most common methylation frequency was detected in the polycomb group target genes (PCGT) including SFRP1
(70%), MYOD1 (60.8%), HIC1 (61.7%), and SLIT2 (56.7%). In addition, MGMT methylation was detected at a high frequency
(68.3%). RASSF1A, APC, and CDKN2A methylation frequencies were 42.5%, 25%, and 32.8%, respectively. K-means clustering
analysis of the methylation events results in the clustering of the CRC samples into three groups depending on the level of
methylation detected.
Conclusion:
Group II (PCGT methylation and CIMP-negative) methylation signature carried a favorable prognosis for male
patients, whereas older patients with group I rare methylation signature have a potentially poorer clinical outcome.
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