Lack of correlation between expression of retinoic acid receptor-beta and loss of heterozygosity on chromosome band 3p24 in esophageal cancer

Loss of heterozygosity (LOH) on chromosome arm 3p occurs frequently in huma n cancers, including esophageal cancer, suggesting that tumor suppressor ge nes may be located on this chromosome arm. The retinoic acid receptor-beta (RARB) gene is localized on chromosome band 3p24, and its expression is pro gressively lost during esophageal carcinogenesis. Furthermore, growth inhib ition of esophageal cancer cell lines by all-trans retinoic acid has been a ssociated with the constitutive and induced expression of RARE. We therefor e assessed LOH on chromosome arm 3p and RARE expression in esophageal cance r to investigate the mechanism of altered RARE expression during carcinogen esis. We first. analyzed LOH in 65 paired surgical specimens of normal muco sa and esophageal cancer by using 10 microsatellite markers, which resulted in 44 informative cases for subsequent study. LOH on chromosome band 3p24 was found to occur at an overall rate of 36.4% (16/44) by three markers (D3 S1293, THRB, and D3S1283). LOH for these three individual markers was 14.0% , 47.4%, and 20.9%, respectively. Meanwhile, RARE expression was lost in 43 .2% (19/44) of these 44 samples. The loss of RARE expression was not correl ated with LOH on chromosome band 3p24 (gamma = -0.22, -0.069, and -0.02, P = 0.15, 0.78, and 0.9 for D3S1293, THRB, and D3S1283, respectively), althou gh both altered RARE expression and LOH in esophageal cancer were statistic ally significant (P = 0.001 and 0.0001, respectively), indicating that the loss of RARE expression cannot be explained by LOH on 3p24. Genes Chromosom es Cancer 28:196-202, 2000. (C) 2000 Wiley-Liss, Inc.