| Theme | Precancerous Conditions and Cancer High-risk Lesions in the Colorectum | |
|---|---|---|
| Title | Precursor Lesions of Colorectal Cancer and Associated Molecular Changes | |
| Publish Date | 2010/09 | |
| Author | Takeshi Sawada | Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine |
| Author | Fumio Itoh | Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine |
| [ Summary ] | Recent advances in molecular genetics have shown that colorectal cancer (CRC) is a heterogeneous disease which develops through diverse molecular pathways. The adenoma-carcinoma sequence (chromosomal instability pathway), caused by sequential accumulations of mutations in oncogenes and tumor suppressor genes (such as APC, Kras, p 53) has been proposed as a genetic model for CRC. However, a subset of sporadic CRCs exhibit both high levels of microsatellite instability and methylation of multiple CpG islands, a phenomenon known as CpG island methylator phenotype. This CRC subset pathway is called the "serrated-neoplasia pathway" because its precursor lesions are typically serrated. Additionally, classification of CRC based on integrated genetic and epigenetic analysis suggests the presence of another distinct subclass. Although the third subclass is heterogeneous, the prognosis is worse, with lower responsiveness to chemotherapy. This subclass may arise from villous adenomas, but perhaps also from serrated adenomas. We also describe genetic and epigenetic changes in hereditary non-polyposis colon cancer, familial adenomatous polyposis and MYH-associated polyposis. |
|