The human homologue of unc-93 maps to chromosome 6q27 – characterisation and analysis in sporadic epithelial ovarian cancer

The human homologue of unc-93 (UNC93A) in C. elegans was identified to be within the interval of allele loss centromeric to D6S149. This gene is 24.5 kb and comprises of 8 exons. There are two transcripts with the shorter one due to splicing out of exon 4. It is expressed in testis, small intestine, spleen, prostate, and ovary. In a panel of 8 ovarian cancer cell lines, UNC93A expression was detected by RT-PCR which identified the two transcripts in 2/8 cell lines. The entire coding sequence was examined for mutations in a panel of ovarian tumours and ovarian cancer cell lines. Mutations were identified in exons 1, 3, 4, 5, 6 and 8. Only 3 mutations were identified specifically in the tumour. These included a c.452G>A (W151X) mutation in exon 3, c.676C>T (R226X) in exon 5 and c.1225G>A(V409I) mutation in exon 8. However, the mutations in exon 3 and 5 were also present in 6% and 2% of the normal population respectively. The UNC93A cDNA was shown to express at the cell membrane and encodes for a protein of 60 kDa.These results suggest that no evidence for UNC93A as a tumour suppressor gene in sporadic ovarian cancer has been identified and further research is required to evaluate its normal function and role in the pathogenesis of ovarian cancer.Ovarian cancer is the most frequent cause of death from gynaecological malignancies in the Western World [1]. Epithelial ovarian cancer constitutes 70–80% of ovarian cancer and encompasses a broad spectrum of lesions, ranging from localised benign tumours and neoplasms of borderline malignant potential to invasive adenocarcinomas. The p53 gene has been found to be frequently mutated (50%) in sporadic malignant ovarian tumours [2]. The BRCA1 and BRCA2 genes are mutated in a proportion of patients with familial breast/ovarian cancer [3]. However, familial ovarian cancer accounts only for 5–10% of all ovarian tumours [4]. In tumours from patients with sporadic ovarian cancer, only five mutations in the BRCA1 gene and four in the