PMID- 10597320 OWN - NLM STAT- MEDLINE DCOM- 20000104 LR - 20061115 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 18 IP - 50 DP - 1999 Nov 25 TI - Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers. PG - 7180-3 AB - We previously reported the presence of mitotic check-point impairment in about 40% of lung cancer cell lines. To gain an insight into the molecular basis of this impairment, we examined 49 lung cancer specimens for alterations in the hMAD1 mitotic checkpoint gene and identified a somatic, non-conservative missense mutation, which substitutes alanine (GCG) for threonine (ACG) at codon 299, together with a number of amino acid substituting, single nucleotide polymorphisms. This is the first demonstration of hMAD1 mutation in any type of human cancers. The present finding marks hMAD1 as a potential target, although with low frequency, for genetic alterations in lung cancer. Thus, further studies of hMAD1 dysfunction caused by other mechanisms appear to be warranted, as well as potential involvement of other components of the mitotic checkpoint. FAU - Nomoto, S AU - Nomoto S AD - Laboratory of Ultrastructure Research, Aichi Cancer Center Research Institute, Nagoya, Japan. FAU - Haruki, N AU - Haruki N FAU - Takahashi, T AU - Takahashi T FAU - Masuda, A AU - Masuda A FAU - Koshikawa, T AU - Koshikawa T FAU - Takahashi, T AU - Takahashi T FAU - Fujii, Y AU - Fujii Y FAU - Osada, H AU - Osada H FAU - Takahashi, T AU - Takahashi T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Carrier Proteins) RN - 0 (Cell Cycle Proteins) RN - 0 (DNA Primers) RN - 0 (MAD1L1 protein, human) RN - 0 (Nuclear Proteins) RN - 0 (Phosphoproteins) RN - 0 (Repressor Proteins) SB - IM MH - Base Sequence MH - *Carrier Proteins MH - Cell Cycle Proteins MH - DNA Primers MH - Humans MH - Lung Neoplasms/*genetics MH - Mitosis/*genetics MH - *Mutation MH - Nuclear Proteins/*genetics MH - Phosphoproteins/*genetics MH - *Repressor Proteins EDAT- 1999/12/22 00:00 MHDA- 1999/12/22 00:01 CRDT- 1999/12/22 00:00 PHST- 1999/12/22 00:00 [pubmed] PHST- 1999/12/22 00:01 [medline] PHST- 1999/12/22 00:00 [entrez] AID - 10.1038/sj.onc.1203141 [doi] PST - ppublish SO - Oncogene. 1999 Nov 25;18(50):7180-3. doi: 10.1038/sj.onc.1203141.