Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers

The mitotic checkpoint is thought to be essential for ensuring accurate chr omosome segregation by implementing mitotic delay in response to a spindle defect. To date, however, very little data has become available on the defe cts of the mitotic checkpoint in human cancer cells, In the present study, impaired mitotic checkpoint was found in four (44%) of nine human lung canc er cell lines. To our knowledge, this is the first demonstration of frequen t impairment of the mitotic checkpoint in this leading cause of cancer deat hs. iis an initial step towards elucidation of the underlying mechanism, we further undertook a search for mutations in a key component of the mitotic checkpoint, known as hsMAD2, and its immediate downstream molecule, p55CDC , No such mutations were found, however, in either 21 lung cancer cell line s or 25 primary lung cancer cases, although we could identify silent polymo rphisms and the transcribed and processed hsMAD2 pseudogene that was subseq uently mapped at 14q21-q23, The present observations appear to warrant furt her investigations, such as search for alterations in other components, to better understand the molecular pathogenesis of this fatal disease, and war n against potential misinterpretation when performing mutational analyses f or other cancer types based on cDNA templates.