Somatic mutation of the hBUB1 mitotic checkpoint gene in primary lung cancer.

摘要: Mutations in mitotic checkpoint genes have been detected several human cancers, and these cancers exhibit chromosomal instability. Aneuploid stem cells seem to result from instability reported many lung cancers. To determine whether alteration of regulators is involved carcinogenesis tumor progression primary cancer, we screened the genomic DNA sequence 30 cancer cell lines tumors for a mutation hBUB1 gene. First, designed 26 sets intron-based primers amplify each 25 exons gene examine entire coding region Using primers, performed polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis as well direct sequencing Three different nucleotide substitutions were some follows. The one adenocarcinoma contained somatic missense mutation, cytosine-to-guanine substitution codon 51 exon 5 that resulted histidine-to-aspartic acid amino substitution. three thymine-to-cytosine 430 12, which did not an amino-acid We unable 12 was or silent because matched normal tissue available. A 93 4, guanine-to-thymine substitution, found line tumor. This first report cancer. presence point consistent with hypothesis development Because frequency mutations low, future studies should focus on other mechanisms inactivation © 2000 Wiley-Liss, Inc.