Gene promoter hypermethylation in tumors and serum of head and neck cancerpatients

Citation
M. Sanchez-cespedes et al., Gene promoter hypermethylation in tumors and serum of head and neck cancerpatients, CANCER RES, 60(4), 2000, pp. 892-895
Citations number
27
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
60
Issue
4
Year of publication
2000
Pages
892 - 895
Database
ISI
SICI code
0008-5472(20000215)60:4<892:GPHITA>2.0.ZU;2-S
Abstract
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.