CDKN2A Hypermethylation and Synchronous Bilateral Colorectal Cancer

The cyclin-dependent kinase inhibitor 2A protein, also known as p16,is a tumor suppressor protein encoded by the CDKN2A gene. CDKN2A promoter methylation is frequently observed in colorectal cancer (CRC) tissues and has been associated with bad prognosis and elevated risk of cancer recurrence. Moreover, CDKN2A methylation is detectable in the circulating free serum DNA and has been proposed as a follow-up marker to monitor for CRC recurrence. Over the past five years we have screened more than100 sporadic CRC samples for aberrant DNA methylation of disease-related genes, observing that CDKN2A promoter hypermethylatio was present in almost 20% of the m(18samples). Very interestingly, only one out of 18 CDKN2A hypermethylated CRC samples showed CDKN2A hypermethylation also in the adjacent healthy colonic mucosa, while the other 17 samples showed no detectable amount of methylation in the analyzed healthy mucosa tissues. Further characterization of the one patient showing CDKN2A hypermethylation in the mucosa adjacent to the CRC lesion revealed that the patient had asynchronous bilateral colorectal cancer, and particularly a scarcely differentiated adenocarcinoma in the right colon and a sigmoid mucinous adenocarcinoma with lymph-node metastasis. Both CRC lesions were characterized by CDKN2A promoter hypermethylation. Our present screening supports literature evidence of the association between CDKN2A methylationandCRCrecurrence.The analysis of serum DNA is currently ongoing in our cohort searching for correlation between CDKN2A methylation and clinico-pathological findings.