A single-nucleotide polymorphism of SMARCB1 in human breast cancers

The gene SMARCB1 has been considered a candidate for a tumor-suppressor gene. Nucleotide alterations in SMARCB1 have been reported, primarily in association with malignant rhabdoid tumor cases. We carried out a search for mutations in SMARCB1 in 60 human gastro-intestinal tract carcinoma cases, 122 breast cancer cases, and 36 human cancer cell lines. A single-nucleotide polymorphism (SNP) at codon 152 with an amino acid change (Asn to Asp) was found in 2 of 122 (1.6%) breast cancer cases, and another SNP at codon 299 without an amino acid change was found in tumor and normal tissues from 7 (5.7%) cases. Codons 152 and 299 of SMARCB1 are localized near or within the binding site for the cMYC protein. The amount of immunoprecipitated cMYC protein was reduced in two different cell lines expressing the codon 152 polymorphic SMARCB1 clone compared with those expressing wild-type SMARCB1, regardless of the identical expression of SMARCB1 protein in both cell lines. Therefore, the SNP at codon 152 is considered to be one of the coding SNPs that alters the SMARCB1-cMYC complex, which regulates various tumor-suppressor related genes against cancer. In addition, we identified three types of splicing isoforms, a 27-bp deleted gene, a 51-bp inserted gene, and a consensus gene, in both carcinoma tissues and in normal tissues; however, no clinical significance was observed for those isoforms. We found a nucleotide change at codon 152 of SMARCB1 that may alter the amount of immunoprecipitated cMYC protein, but we finally determined that SMARCB1 is highly conserved in human solid carcinomas.