Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

TY - JOUR

T1 - Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

AU - Gao, S

AU - Worm, J

AU - Guldberg, P

AU - Eiberg, H

AU - Krogdahl, A

AU - Sørensen, J A

AU - Liu, C-J

AU - Reibel, J

AU - Dabelsteen, Erik

PY - 2004/8/16

Y1 - 2004/8/16

N2 - The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours was examined for loss of heterozygosity (LOH) at three markers surrounding DBCCR1 and for hypermethylation of the DBCCR1 promoter, using methylation-specific PCR and methylation-specific melting-curve analysis. LOH was found in 10 of 31 cases (32%), and DBCCR1 hypermethylation was present in 15 of 34 cases (44%). Hypermethylation of DBCCR1 was also present in three of seven epithelial tissues adjacent to the tumours, including two hyperplastic and one histologically normal epithelia. Furthermore, of four oral leukoplakias with dysplasia, one showed LOH at 9q33 and two showed DBCCR1 hypermethylation. These data suggest that LOH at 9q33 and hypermethylation of the DBCCR1 promoter are frequent and possibly early events in oral malignant development.

AB - The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours was examined for loss of heterozygosity (LOH) at three markers surrounding DBCCR1 and for hypermethylation of the DBCCR1 promoter, using methylation-specific PCR and methylation-specific melting-curve analysis. LOH was found in 10 of 31 cases (32%), and DBCCR1 hypermethylation was present in 15 of 34 cases (44%). Hypermethylation of DBCCR1 was also present in three of seven epithelial tissues adjacent to the tumours, including two hyperplastic and one histologically normal epithelia. Furthermore, of four oral leukoplakias with dysplasia, one showed LOH at 9q33 and two showed DBCCR1 hypermethylation. These data suggest that LOH at 9q33 and hypermethylation of the DBCCR1 promoter are frequent and possibly early events in oral malignant development.

KW - Adult

KW - Aged

KW - Carcinoma, Squamous Cell

KW - Cell Transformation, Neoplastic

KW - Chromosomes, Human, Pair 9

KW - DNA Methylation

KW - Female

KW - Genes, Tumor Suppressor

KW - Humans

KW - Loss of Heterozygosity

KW - Male

KW - Middle Aged

KW - Mouth Neoplasms

KW - Precancerous Conditions

KW - Promoter Regions, Genetic

KW - Tumor Suppressor Proteins

U2 - 10.1038/sj.bjc.6601980

DO - 10.1038/sj.bjc.6601980

M3 - Journal article

C2 - 15226771

SN - 0007-0920

VL - 91

SP - 760

EP - 764

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

IS - 4

ER -