Mutations in the ST7/RAY1/HELG locus rarely occur in primary colorectal, gastric, and hepatocellular carcinomas

Abstract

Human cancers frequently show a loss of heterozygosity on chromosome 7q31, which indicates the existence of broad-range tumour-suppressor gene(s) at this locus. Truncating mutations in the ST7 gene at this locus are seen frequently in primary colon cancer and breast cancer cell lines. Therefore, the ST7 gene represents a novel candidate gene for the tumour suppressor at this locus. However, more recent studies have reported that ST7 mutations are infrequent or absent in primary cancer and cell lines. To ascertain the frequency of mutations of the ST7 gene in cancer cells, we examined mutations in the ST7 coding sequence in 48 colorectal, 48 gastric, and 48 hepatocellular carcinomas using polymerase chain reaction-single-strand conformational polymorphism and direct sequencing. We detected somatic mutations, which were located near the exon-intron junction in intron 8, in only three out of 144 cases. We conclude that mutations in the ST7 gene are rare in primary colorectal, gastric, and hepatocellular carcinomas.

Figure 1

Representative example of an ST7 frameshift mutation. (A) SSCP analysis of the intron 8–exon 9 junction of the ST7 gene. The solid arrow indicates a shifted band in the tumour sample. T: tumour samples; N: corresponding normal tissue samples. (B) Sequence analysis. The open arrow indicates deletions in the polypyrimidine tract within the splice-acceptor site of intron 8 (−3 nucleotides from exon 9). The number of nucleotides deleted ranged from one to three.

Figure 2

Representative example of a 1-bp substitution in the coding sequence of the ST7 gene. (A) SSCP analysis of the intron 8–exon 9 junction of the ST7 gene. The solid arrow indicates the shifted band that was predicted to carry substitutions, in both the tumour and corresponding normal tissue sample. The open arrow indicates another allele without a substitution. T: tumour samples; N: corresponding normal tissue samples; CRC=colorectal cancer. (B) Sequence analysis. The open arrow indicates a one-nucleotide substitution in exon 9 of the ST7 gene.