Mutation analysis of hBUB1 in aneuploid HNSCC and lung cancer cell lines

Aneuploidy is frequently observed in many types of human cancer cells, sugg esting that mutations of genes required for chromosomal stability may occur in human tumors, The BUB gene is a component of the mitotic checkpoint in budding yeast that delays anaphase in the presence of spindle damage thus i ncreasing the probability of successful delivery of a euploid genome to eac h daughter cell. Recently, human homologues of the BUB gene were identified and mutant alleles of hBUB1 were detected in two colorectal tumor cell lin es. Transfection of one mutant allele led to dominant disruption of the mit otic checkpoint control in a euploid cell, suggesting that aneuploidy in so me tumors could be due to defects in the mitotic checkpoint, We analyzed th e entire coding sequence of hBUB1 for mutation in 31 head and neck squamous cell carcinoma (HNSCC) and lung cancer cell lines, most with severe aneupl oidy. We found expression of the hBUB1 gene in all cell lines and only a si ngle nucleotide substitution in one cell line without a resultant change in amino acid sequence. Our study demonstrates that hBUB1 is rarely a target for genetic alterations in turners of the respiratory tract. (C) 1999 Elsev ier Science Ireland Ltd, All rights reserved.