Promoter hypermethylation is an important. pathway for repression of gene t
ranscription in cancer cells. We analyzed aberrant DNA methylation at four
genes in primary tumors from 95 head and neck cancer patients and then used
the presence of this methylation as a marker for cancer cell detection in
serum DNA, These four genes were tested by ethylation-specific PCR and incl
uded: p16 (CDKN2A) O-6-methylguanine-DNA-methyltransferase, glutathione S-t
ransferase P1, and death-associated protein kinase (DAP-kinase), Fifty-five
% (52 of 95) of the primary tumors displayed promoter hypermethylation in
at least one of the genes studied: 27% (26/95) at p16, 33% (31 of 95) at O-
6-methylguanine-DNA-methyltransferase; and 18% (17 of 92) at DAP-kinase. No
promoter hypermethylation was observed at the glutathione S-transferase P1
gene promoter. We detected a statistically significant correlation between
the presence of DAP-kinase gene promoter hypermethylation and lymph node i
nvolvement (P = 0.014) and advanced disease stage (P = 0.016). In 50 patien
ts with paired serum available for epigenetic analysis, the same methylatio
n pattern was detected in the corresponding serum DNA of 21 (42%) cases. Am
ong the patients with methylated serum DNA, 5 developed distant metastasis
compared with the occurrence of metastasis in only 1 patient negative for s
erum promoter hypermethylation (P = 0.056). Promoter hypermethylation of ke
y genes in critical pathways is common in head and neck cancer and represen
ts a promising serum marker for monitoring affected patients.