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[Cancer Research 62, 13-17, January 1, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Genetic and Epigenetic Inactivation of Mitotic Checkpoint Genes hBUB1 and hBUBR1 and Their Relationship to Survival1

Masayoshi Shichiri2, Keigo Yoshinaga, Hisashi Hisatomi, Kenichi Sugihara and Yukio Hirata

Departments of Clinical and Molecular Endocrinology [M.S., Y.H.] and Digestive Surgery [K.Y., K.S.], Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo 113-8519, and Molecular and Chromosome Analysis Center, Special Reference Laboratories, Tokyo 191-0002 [H.H.], Japan

Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1, were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers and their neighboring normal tissues. Our results reveal a new hBUB1 missense mutation (Ala130Ser) but not any hBUBR1 coding sequence mutations. hBUB1 and hBUBR1 mRNA levels were reduced to <10% of the neighboring normal tissues in 3 of 103 and 3 of 109 carcinomas, respectively, and to <50% in 7 and 7 carcinomas, whereas the overall expression levels were markedly higher in cancers than in normal tissues. Carcinomas with reduced hBUB1 and/or hBUBR1 mRNA levels, as well as the colon carcinoma harboring the hBUB1 mutation, were associated with lymph node metastasis (P < 0.005) and shorter relapse-free survival after surgery (P = 0.006). Thus, hBUB1 and hBUBR1 may contribute to a specific driving force in tumor metastasis and progression as a result of nonmutational, as well as mutational, inactivation.




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Copyright © 2002 by the American Association for Cancer Research.