Sessile serrated polyps (SSPs), notorious for being difficult to detect and for their potential to become malignant colorectal tumors, appear to be caused by a single oncogenic mutation, a finding that could lead to better early detection of some colorectal cancers through noninvasive stool testing, investigators say.
Using a comprehensive battery of genomic testing and DNA methylation profiling, David Jones, PhD, of the Oklahoma Medical Research Foundation in Oklahoma City and his colleagues compared SSPs with familial adenomatous polyps (FAPs), and found that the V600E mutation in BRAF (V-Raf Murine Sarcoma Viral Oncogene Homolog B) was the sole cancer-causing mutation in SSPs.
They also found a distinct DNA methylation pattern unique to SSPs.
“These SSP-specific methylation patterns effectively distinguish SSP from adenomatous polyps, which could be important for both diagnosis and treatment. It also suggests that the BRAF-V600E mutation directly or indirectly results in the remodeling of the epigenome and that this may set a stage for tumor progression,” they wrote in the open-access journal PLOS One.
Approximately one-third of sporadic colorectal cancers, which account for about 95% of all colorectal malignancies, are thought to arise from premalignant serrated lesions, including SSPs, hyperplastic polyps, and traditional serrated adenomas, the authors noted.
Although SSPs and traditional serrated adenomas both have significant potential for malignant transformation, SSPs are much more common, making them important targets for research, diagnosis, and possible interventions.
“Previous surveys of cancer-associated mutations in SSP samples, through targeted analysis of limited known mutations, identified the BRAF-V600E as the key mutation in this disease. However, it is not clear whether other mutations in the same samples contribute to the etiology of this disease,” Dr. Jones and his associates wrote.