Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival.

Abstract:

: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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Shichiri M,Yoshinaga K,Hisatomi H,Sugihara K,Hirata Y

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

13-7

issue

1

eissn

0008-5472

issn

1538-7445

journal_volume

62

pub_type

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