Promoter hypermethylation in Indian primary oral squamous cell carcinoma.
We evaluated promoter hypermethylation of a panel of tumor suppressor genes as a means to detect epigenetic alterations in oral squamous cell carcinomas (OSCC) of Indian-origin and compare with North-American head and neck squamous cell carcinomas (HNSCC). Quantitative-methylation-specific PCR was used to investigate the promoter methylation status of DCC, EDNRB, p16(INK4a) and KIF1A in 92 OSCC, and compared to 48 paired normal tissues and 30 saliva and sera samples from healthy control subjects. Aberrant methylation of at-least one of these genes was detected in 74/92 (80.4%) OSCC; 72.8% at EDNRB, 71.7% at KIF1A, 47.8% at p16(INK4a) and 58.7% at DCC; and in 5 of 48 (10.4%) normal oral tissues. None of the saliva and sera samples from controls exhibited DNA methylation in these four target genes. Thirty-two of 72 node positive cases harbored p16(INK4a) and DCC hypermethylation (p = 0.005). Thus, promoter hypermethylation in genes analyzed herein is a common event in Indian OSCC and may represent promising markers for the molecular staging of OSCC patients. We found higher frequency of p16(INK4a) methylation (47.8%) in this Indian cohort in comparison with a North-American cohort (37.5%). In conclusion, aberrant methylation of EDNRB, KIF1A, DCC and p16(INK4a) genes is a common event in Indian OSCC, suggesting that epigenetic alterations of these genes warrant validation in larger studies for their potential use as biomarkers.
Kaur
Jatinder
J
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Demokan
Semra
S
Tripathi
Satyendra Chandra
SC
Macha
Muzafar Ahmad
MA
Begum
Shahnaz
S
Califano
Joseph A
JA
Ralhan
Ranju
R
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D007194:India; D016547:Kinesins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D044023:Receptor, Endothelin B / Q000235:genetics
C094065:KIF1A protein, human; D044023:Receptor, Endothelin B; D016547:Kinesins
Head Neck. 2009 Nov;31(11):1423-30
19431196
Cancer Lett. 2007 Feb 8;246(1-2):139-48
16581180
Clin Cancer Res. 2003 Apr;9(4):1370-5
12684406
Cancer. 1992 Mar 15;69(6 Suppl):1589-91
1540900
Clin Cancer Res. 2008 Jan 1;14(1):97-107
18172258
Oncology. 2007;72(5-6):357-63
18187958
Curr Vasc Pharmacol. 2007 Jul;5(3):239-48
17627567
Int J Cancer. 2003 May 20;105(1):41-6
12672028
Oncol Rep. 2006 Jan;15(1):167-72
16328051
Int J Mol Med. 2004 Nov;14(5):807-11
15492849
Cancer Genet Cytogenet. 2007 Feb;173(1):31-7
17284367
Ann N Y Acad Sci. 2003 Mar;983:120-30
12724217
Hum Pathol. 2008 Mar;39(3):452-8
18261630
Oncogene. 2002 Aug 12;21(35):5380-7
12154400
Int J Cancer. 2002 Apr 10;98(5):651-5
11920632
J Biomech. 2008 Nov 14;41(15):3196-201
18829030
Cancer Surv. 1995;24:3-17
7553661
Br J Cancer. 2008 Jul 22;99(2):357-63
18594522
Clin Cancer Res. 2002 Oct;8(10):3164-71
12374684
Nat Med. 1995 Jul;1(7):686-92
7585152
Cancer Res. 2002 Sep 15;62(18):5295-300
12234999
Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):414-20
18268126
Cancer Res. 2008 Apr 15;68(8):2661-70
18413733
N Engl J Med. 2003 Nov 20;349(21):2042-54
14627790
CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
18287387
Oncol Rep. 2006 Feb;15(2):507-11
16391877
Clin Cancer Res. 2007 Apr 1;13(7):2046-53
17404085
J Cancer Res Clin Oncol. 2003 Nov;129(11):642-50
14586645
J Clin Pathol. 2003 Jan;56(1):52-5
12499435
Cancer Res. 2006 Oct 1;66(19):9401-7
17018594
Oral Oncol. 2004 Feb;40(2):145-53
14693237
Int J Cancer. 2008 Jun 1;122(11):2498-502
18302152
Lancet Oncol. 2006 Jan;7(1):77-82
16389187