Analysis of the ANA gene as a candidate for the chromosome 21q oval cancersusceptibility locus

Loss of heterozygosity (LOH) on the long arm of chromosome 21 (21q) is obse rved in several human malignancies. We identified novel tumour suppressor l oci on this region in primary oral squamous cell carcinomas (OSCCs), To fur ther determine the role of 21q deletions in oral cavity tumorigenesis, 63 O SCCs were examined for LOH at 21q using 7 microsatellite markers. LOH was o bserved in 32 of 63 cases (50.8%) that were informative for at least one of the loci analysed. Two distinct deleted regions were identified at chromos omal region 21q11.1. The possible involvement of ANA (abundant in neuroepit helium area), a candidate tumour suppressor gene (TSG) located on 21q11.2-2 1.1,was also evaluated for 20 OSCCs and 9 OSCC-derived cell lines. 60% of t umours (12/20) and 88.9% (8/9 cell lines) showed absent or reduced mRNA gen e expression; only one OSCC case had a nucleotide substitution in the ANA g ene. Interestingly, the frequency of the suppressed ANA mRNA expression was greater in stage IV tumours than in earlier stages. In addition, re-expres sion of the ANA gene mRNA was induced in 4 cell lines after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. These findings demonstra te that there may be at least 2 distinct TSGs on 21q11.1; loss of ANA gene expression could be involved in the progression of human OSCC; and aberrant methylation of the ANA gene promoter may participate in the transcriptiona l silencing of the gene in oral cancer cells. (C) 2001 Cancer Research Camp aign htip://www.bjcancer.com.