Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma
Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma
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DOI：
10.1038/sj.bjc.6601980
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发表时间：
2004-08-16
影响因子：
8.8
通讯作者：
Dabelsteen, E
中科院分区：
文献类型：
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作者：
Gao, S;Worm, J;Dabelsteen, E
位于染色体9 q33的DBCCR 1基因已被鉴定为候选肿瘤抑制基因，其在膀胱癌中经常被启动子超甲基化靶向。在这里，我们研究了DBCCR 1在口腔鳞状细胞癌的发展可能参与。采用甲基化特异性PCR和甲基化特异性熔解曲线分析，检测了34例肿瘤DNA中DBCCR 1周围3个标记的杂合性丢失（洛）和DBCCR 1启动子的超甲基化。洛缺失率为32%（10/31），甲基化率为44%（15/34）。DBCCR 1的超甲基化也存在于肿瘤附近的七个上皮组织中的三个，包括两个增生和一个组织学正常的上皮。此外，在4例口腔白斑伴异型增生中，1例在9 q33出现洛，2例出现DBCCR 1高甲基化。这些数据表明，洛在9 q33和高甲基化的DBCCR 1启动子是常见的，并可能在口腔恶性发展的早期事件。
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.