Frequent Deletion of BRG1 Locus at 19p13 Predicts Recurrence and Previous Cancer History in Oral Squamous Cell Carcinomas

抄録

Activation of oncogenes and inactivation of tumor suppressor genes (TSGs) is a critical step during carcinogenesis. Inactivation of TSGs occurs through deletion of one allele and mutation in the other allele or decreased mRNA expression. Loss of heterozygosity (LOH) analysis is a sensitive method to detect deletions of specific chromosome regions, which are considered to harbor putative TSGs. By this method we previously demonstrated the frequent deletions of several chromosomal loci and identified candidate TSGs such as ING1, ING3, ING4, Caspase-6 and BRG1 in head and neck cancer. On the other hand, recent researches showed that alterations of chromosomal loci and genes could be used as a predictive marker for the prognosis of the patients, for the behaviour of the tumor and its response to treatments such as chemotherapy and radiotherapy. We recently detected high allelic loss of 19p13 region and identified BRG1 gene as a candidate TSG in 39 oral cancer samples. In the current study, we analyzed the clinicopathological data of the patients and compared with the deletion at BRG1 locus. Our results demonstrated that deletion at BRG1 locus could predict the recurrence, secondary primary cancer, or previous cancer history in oral cancer. Retention of LOH at 19p13 region suggested a high recurrence and secondary primary or previous cancer history. We also detected a higher LOH ratio in cases with smoking and alcohol consumption. The current study suggests that LOH at BRG1 locus could be used as a predictive marker in oral cancer.