Mutation analysis of the DBC2 gene in sporadic and familial breast cancer

The expression of the recently identified tumor suppressor gene, DBC2 ( Deleted in Breast Cancer 2), is frequently extinguished in breast cancer cells or tissues. Mutation analysis of the essential promoter region, all exons and exon/intron boundaries of the DBC2 gene was performed in 100 sporadic breast cancer cases by PCR-SSCP, and DHPLC, followed by direct sequencing. An additional 17 breast cancer families, who were negative for the BRCA1/2 mutations, were analyzed by direct sequencing. Three novel mutations were observed in the promoter and 5'- untranslated region ( UTR) of the gene; a germ-line G > A transition in the promoter at nt - 238 from the transcription start site, and two tumor- specific mutations at nt - 121C > T and nt +48G > A. No deleterious mutations were detected in the coding sequence of the gene in familial and sporadic breast cancer cases. The sequence variations found within the promoter and 5'- UTR region of the gene warrant expression analysis and screening more tumor samples at this region.