Frequency of genetic and epigenetic alterations of p14ARF and p16INK4A in head and neck cancer in a Hungarian population.
Occurrence of genetic and epigenetic alterations affecting p14ARF and p16INK4A were investigated in tumour samples of 37 oral (OSCC) and 28 laryngeal squamous cell cancer (LSCC) patients, and compared to exfoliated buccal epithelial cells of 68 healthy controls. Presence of deletions and mutations/polymorphisms affecting exons were examined using sequencing. Methylation status of promoters was assessed by methylation-specific PCR. Chi-square and Fisher's exact tests were used to compare frequency of events. Exon deletions were found in four controls, one OSCC and 22 LSCC patients; the latter significantly differed from controls (p < 0.001). Only two mutations (T24610A and C24702A) were in p16 exon 1 of two OSCC patients. Polymorphisms G28575A (Ala140Thr), G31292C (C540G) and G28608A were found in both patient groups. The p14 promoter was unmethylated in 86.7 % of OSCC and in 85.7 % of LSCC patients; for the p16 promoter these rates were 69.0 % and 76.2 % for OSCC and LSCC patients, respectively. Combining the two patient groups, unmethylated promoter was significantly less frequent in case of both p14 and p16 (p = 0.043 and p = 0.001, respectively) compared to the control group. In summary, exon deletion may be important in LSCC, while promoter methylation was relatively frequent in both patient groups.
Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, H-4032, Debrecen, Nagyerdei krt. 98, Hungary.
Andrea
A
Kis
Tímea Zsófia
TZ
Tatár
Tamás
T
Gáll
Róbert
R
Boda
Ildikó
I
Tar
Tamás
T
Major
Pál
P
Redl
Lajos
L
Gergely
Krisztina
K
Szarka
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D020868:Gene Silencing; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007822:Laryngeal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D015996:Survival Rate; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF