Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation.
BACKGROUND
Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer.


METHODS
The promoter methylation status of the DNA repair gene MGMT and the tumor suppressor genes CDKN2A and RASSF1 were evaluated by methylation-specific PCR in 88 primary oral and pharyngeal tumors and correlated with survival and tumor recurrence. Quantitative MGMT methylation was also assessed.


RESULTS
29.6% of the tumors presented with MGMT methylation, 11.5% with CDKN2A methylation and 12.1% with RASSF1 methylation. MGMT promoter methylation was significantly associated with poorer overall and disease-free survival. No differences in methylation status of MGMT and RASSF1 with HPV infection, smoking or drinking habits were observed. A significant inverse trend with the amount of MGMT methylation and overall and disease-free survival was observed (ptrend = 0.002 and 0.001 respectively).


CONCLUSIONS
These results implicate MGMT promoter methylation as a possible biomarker for oral and pharyngeal cancer prognosis. The critical role of MGMT in DNA repair suggests that defective DNA repair may be correlative in the observed association between MGMT promoter methylation and tumor recurrence. Follow-up studies should include further quantitative MSP-PCR measurement, global methylation profiling and detailed analysis of downstream DNA repair genes regulated by promoter methylation.
Taioli
Emanuela
E
University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA, USA.
Ragin
Camille
C
Wang
Xiao-Hong
XH
Chen
Jiangying
J
Langevin
Scott M
SM
Brown
Ashley R
AR
Gollin
Susanne M
SM
Garte
Seymour
S
Sobol
Robert W
RW
D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D010610:Pharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011401:Promoter Regions, Genetic; D012008:Recurrence; D013534:Survival; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes