Source: The Sixth Affiliated Hospital
Written by: Jian Wenyang
Translated by: Luo Yanxin
Edited by: Wang Dongmei

Colorectal cancer develops from the accumulation of DNA mutations and epigenetic changes that alter the expression or function of oncogenes and tumor-suppressor genes. A common epigenetic change found in cancer is aberrant DNA methylation, a biochemical change in the DNA of gene promoters that silences the expression of genes. There is considerable molecular heterogeneity among colorectal tumors, which appears to arise as polyps progress to cancer. This heterogeneity results in different pathways to tumorigenesis. Although epigenetic and genetic alterations have been detected in conventional tubular adenomas, little is known about how these affect progression to CRC.

A study led by Dr. Luo Yanxin, MD PhD at Sun Yat-sen University and Dr. William M. Grady MD at the Fred Hutchinson Cancer Research Center conducted genome-wide array-based studies and comprehensive data analyses of aberrantly methylated loci in normal colon tissue, colon adenomas, and cancers using cutting-edge technologies and found genome-wide alterations in DNA methylation in the non-tumor colon mucosa adjacent to tubular adenomas and cancers. Three classes of cancers and 2 classes of adenomas were identified based on their DNA methylation patterns.

In this study, the adenomas separated into classes of high-frequency methylation (adenoma-H), and low-frequency methylation (adenoma-L). Within the adenoma-H class a subset of adenomas had mutant KRAS. Additionally, the adenoma-H class had DNA methylation signatures similar to those of cancers with low or intermediate levels of methylation, whereas the adenoma-L class had methylation signatures similar to that of non-tumor colon tissue. “This study identifies novel molecular subgroups of colon polyps that may be the polyps that do not progress or that progress to microsatellite stable colorectal cancers. These results have the potential to lead to more precise risk stratification methods and to improve the cost effectiveness of colorectal cancer screening”, said Dr. Luo Yanxin, a physician-scientist at the department of colorectal surgery at The Sixth Affiliated Hospital of SYSU.

The result of this study was published in Gastroenterology:
www.ncbi.nlm.nih.gov/pubmed/24793120