Mutational analysis of the NM23.H1 gene in human breast cancer

NM23.H1 is a protein connected with tumor progression. Loss of heterozygosi ty and reduced expression of the gene have been associated with poor progno sis and increased incidence of metastases in many epithelial tumors. The ai m of this study was to detect the presence of NM23.H1 point mutations or sm all deletions in hum an breast carcinomas by using the single-strand-confor mation polymorphism (SSCP) technique. Mutational analysis was performed on 76 breast tumors, 10 of which had allelic deletion of the gene. The NM23.H1 mRNA content also was evaluated in each sample. Only a C-to-A transversion leading to a stop codon was found ill the 5' untranslated region of exon 1 . A polymorphic SSCP pattern was identified in exon 1; direct sequencing sh owed a C-to-T transition 30 nucleotides upstream from the 5' splice site fl anking exon 1. None of the tumors analyzed presented both alleles inactivat ed. Our results suggest that NM23.H1 is rarely inactivated by point mutatio ns. (C) 2000 Elsevier Science inc. All rights reserved.