Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 97, Issue 2, Pages 710-715Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.97.2.710
Keywords
-
Categories
Funding
- NCI NIH HHS [CA62924, P50 CA062924] Funding Source: Medline
- NIDDK NIH HHS [1-T32-DK07713, T32 DK007713] Funding Source: Medline
Ask authors/readers for more resources
Colorectal cancers (CRCs) are characterized by multiple genetic (mutations) and epigenetic (CpC island methylation) alterations, but it is not known whether these evolve independently through stochastic processes. We have recently described a novel pathway termed CpG island methylator phenotype (CIMP) in CRC, which is characterized by the simultaneous methylation of multiple CpC islands, including several known genes, such as p16, hMLH1, and THBS1, We have now studied mutations in K-RAS, p53, DPC4, and TGF beta RII in a panel of colorectal tumors with or without CIMP, We find that CIMP defines two groups of tumors with significantly different genetic lesions: frequent K-RAS mutations were found in CIMP+ CRCs (28/41, 68%) compared with CIMP- cases (14/47, 30%, P = 0.0005). By contrast, p53 mutations were found in 24% (10/41) of CIMP+ CRCs vs. 60% (30/46) of CIMP- cases (P = 0.002), Both of these differences were independent of microsatellite instability. These interactions between CIMP, K-RAS mutations, and p53 mutations were preserved in colorectal adenomas, suggesting that they occur early in carcinogenesis. The distinct combinations of epigenetic and genetic alterations in each group suggest that activation of oncogenes and inactivation of tumor suppressor genes is related to the underlying mechanism of generating molecular diversity in cancer, rather than simply accumulate stochastically during cancer development.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available