Abstract
We previously reported the presence of mitotic checkpoint 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW and Vogelstein B. . 1998 Nature 392: 300–303.
Elledge SJ. . 1998 Science 279: 999–1000.
Gotoh K, Yatabe Y, Sugiura T, Takagi K, Ogawa M, Takahashi T, Takahashi T and Mitsudomi T. . 1999 Carcinogenesis 20: 499–502.
Hardwick KG and Murray AW. . 1995 J. Cell. Biol. 131: 709–720.
Hardwick KG, Weiss E, Luca FC, Winey M and Murray AW. . 1996 Science 273: 953–956.
Hibi K, Yamakawa K, Ueda R, Horio Y, Murata Y, Tamari M, Uchida K, Takahashi T, Nakamura Y and Takahashi T. . 1994 Oncogene 9: 611–619.
Hoyt MA, Totis L and Roberts BTS. . 1991 Cell 66: 507–517.
Jin DY, Spencer F and Jeang KT. . 1998 Cell 93: 81–91.
Lengauer C, Kinzler KW and Vogelstein B. . 1998 Nature 396: 643–649.
Li Y and Benezra R. . 1996 Science 274: 246–248.
Li R and Murray AW. . 1991 Cell 66: 519–531.
Minna JD, Sekido Y, Fong KM and Gazdar AF. . 1997 In: Cancer Principles & Practice of Oncology, 5th edn, Vol.1. DeVita Jr VT, Hellman S and Rosenberg SA. (eds).. Lippincott-Raven: Philadelphia. pp.849–857.
Nagatake M, Takagi Y, Osada H, Uchida K, Mitsudomi T, Saji S, Shimokata K, Takahashi T and Takahashi T. . 1996 Cancer Res. 56: 2718–2720.
Paulovich AG, Toczyski DP and Hartwell LH. . 1997 Cell 88: 315–321.
Rudner AD and Murray AW. . 1996 Curr. Opin. Cell. Biol. 8: 773–780.
Smith AL, Hung J, Walker L, Rogers TE, Vuitch F, Lee E and Gazdar AF. . 1996 Brit. J. Cancer 73: 203–209.
Statistics and Information Department. 1998 Vital Statistics of Japan (1996), Vol.3. Ministry of Health and Welfare: Tokyo. pp.384–411.
Takahashi T, Haruki N, Nomoto S, Masuda A, Saji S, Osada H and Takahashi T. . 1999 Oncogene 18: 4295–4300.
Testa JR. . 1996 In: Lung Cancer: Principles and Practice. Pass HI, Mitchell JB, Johnson DH and Turrisi AT. (eds).. Lippincott-Raven: Philadelphia. pp.55–71.
Washimi O, Nagatake M, Osada H, Ueda R, Koshikawa T, Seki T, Takahashi T and Takahashi T. . 1995 Cancer Res. 55: 514–517.
Acknowledgements
We would like to thank K-T Jeang and R Ishida for helpful discussions and H Ishida and Y Tatematsu for their technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture, Japan.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nomoto, S., Haruki, N., Takahashi, T. et al. Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers. Oncogene 18, 7180–7183 (1999). https://doi.org/10.1038/sj.onc.1203141
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203141
Keywords
This article is cited by
-
Mitotic arrest deficient-like 1 is correlated with poor prognosis in small-cell lung cancer after surgical resection
Tumor Biology (2016)
-
A computational approach to explore the functional missense mutations in the spindle check point protein Mad1
Frontiers in Biology (2013)
-
Mitotic chromosomal instability and cancer: mouse modelling of the human disease
Nature Reviews Cancer (2010)
-
In silico whole-genome scanning of cancer-associated nonsynonymous SNPs and molecular characterization of a dynein light chain tumour variant
Oncogene (2005)
-
On the road to cancer: aneuploidy and the mitotic checkpoint
Nature Reviews Cancer (2005)