Hypermethylation of the Myf-3 gene in colorectal cancers: Associations with pathological features and with microsatellite instability

Myf-3 is the human homologue of the murine Myo-D1 gene involved in muscle-c ell differentiation. Using Southern blot analysis, we examined methylation of Myf-3 in histologically normal colonic mucosae, adenomas and carcinomas from a large series of patients with primary colorectal cancer. Hypermethyl ation of this gene in comparison with normal mucosa was observed in 88% of adenomas and in 99% of carcinomas. The pattern of Myf-3 methylation was sim ilar in different areas of the same tumour, suggesting that methylation imb alances occur before the bulk of clonal-cell expansion. Significantly incre ased levels of Myf-3 methylation were observed in tumours which were more i nvasive, located in the proximal colon or from older patients. Patients who se tumours had extensive methylation showed a trend for shortened survival, though this was probably related to their being more invasive. Extensive m ethylation was significantly more frequent in tumours with microsatellite i nstability. Further work is required to determine whether the hypermethylat ion of Myf-3 observed in colorectal cancers is a specific alteration with f unctional significance or whether it reflects non-specific methylation imba lances occurring early during tumorigenesis. Int. J. Cancer (Pred. Oncol.) 84:109-113, 1999. (C) 1999 Wiley-Liss, Inc.