Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers

We previously reported the presence of mitotic checkpoint impairment in abo ut 40% of lung cancer cell lines. To gain an insight into the molecular bas is of this impairment, we examined 49 lung cancer specimens for alterations in the hMAD1 mitotic checkpoint gene and identified a somatic, non-conserv ative missense mutation, which substitutes alanine (GCG) for threonine (GCG ) at codon 299, together with a number of amino acid substituting, single n ucleotide polymorphisms. This is the first demonstration of hMAD1 mutation in any type of human cancers. The present finding marks hMAD1 as a potentia l target, although with low frequency, for genetic alterations in lung canc er. Thus, further studies of hMAD1 dysfunction caused by other mechanisms a ppear to be warranted, as well as potential involvement of other components of the mitotic checkpoint.