Objective: Human alpha-catenin gene (CTNNA1) on chromosome 5q31 is aberrantly expressed in various types of cancer including epithelial ovarian tumors. Allelic imbalance on this region has also been described in several malignant diseases. In the present work, the role of CTNNA1 as a candidate tumor suppressor gene was studied by comparing protein expression with allelic imbalance in human epithelial ovarian tumors.
Methods: Alpha-catenin protein expression was determined from two areas of 41 tumors, and tissues from these areas were microdissected. After DNA extraction, AI analysis was carried out with eight microsatellite markers.
Results: Altogether, 93% of the tumors (38 of 41) showed allelic imbalance at one or more loci. Two distinct common regions of allelic imbalance were identified, one comprising markers D5S2002 and D5S1995 and the other markers D5S393 and D5S476. Loss of the CTNNA1 gene did not appear to be involved in down-regulation of alpha-catenin in ovarian tumors, since allelic imbalance with a variety of markers, including CTNNA1 associated marker D5S476, was found in tumor samples independently of alpha-catenin expression. Furthermore, allelic imbalance analyses of two different samples from the same tumor revealed genetic heterogeneity.
Conclusions: High allelic imbalance frequency indicates that chromosomal region 5q31 is functionally important in epithelial ovarian cancer. Allelic imbalance occurs at two distinct regions of which one includes the CTNNA1 gene. However, this gene is likely to be inactivated by mechanisms other than allelic imbalance. In addition, genetic heterogeneity observed in these tumors demonstrates the multiclonal nature of epithelial ovarian tumors.