Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer

Mitsuo Sato, Yoshitaka Sekido, Yoshitsugu Horio, Masahide Takahashi, Hidehiko Saito, John D. Minna, Kaoru Shimokata, Yoshinori Hasegawa

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Mitotic checkpoint defects of the cell cycle have been implicated in the development of human cancers. Since hBUB1 and hBUBR1, whose products function in the spindle checkpoint pathway, have been shown to be mutated in a subset of colon cancers with chromosomal instability, we investigated the contribution of these genes to lung cancer development. One hundred and two lung cancer (50 small cell lung cancers and 52 non-small cell lung cancers) and 4 mesothelioma cell line DNAs were analyzed by Southern blot analysis, but no rearrangements or deletions of hBUB1 and hBUBR1 were detected. Using single strand conformation polymorphism analysis, we studied all the 25 exons except exon 1 of the hBUB1 gene in 88 lung cancer DNAs. One lung cancer cell line, NCI-H345, showed a single nucleotide substitution, which resulted in an Arg-to-Gln change at codon 209 (CGA to CAA). Eleven cell line DNAs exhibited a single nucleotide polymorphism in intron 9 of hBUB1, all of which were heterozygous. Similar mutation analysis of hBUBR1 in 47 lung cancer cell line cDNAs revealed a frequent polymorphism at codon 349 (CAA to CGA) leading to a substitution of Gln to Arg but no mutations. Northern blot analyses showed that both hBUB1 and hBUBR1 genes were expressed in all of 31 lung cancer cell lines tested with no significant difference in the expression level. Our results suggest that alterations in hBUB1 and hBUBR1 rarely contributed to the genetic change of lung cancers.

Original languageEnglish (US)
Pages (from-to)504-509
Number of pages6
JournalJapanese Journal of Cancer Research
Volume91
Issue number5
StatePublished - May 2000

Fingerprint

Lung Neoplasms
Mutation
Cell Line
Genes
Codon
Exons
DNA
M Phase Cell Cycle Checkpoints
Chromosomal Instability
Mesothelioma
Small Cell Lung Carcinoma
Human Development
Southern Blotting
Non-Small Cell Lung Carcinoma
Northern Blotting
Colonic Neoplasms
Introns
Single Nucleotide Polymorphism
Cell Cycle
Nucleotides

Keywords

  • HBUB1
  • HBUBR1
  • Lung cancer
  • Mitotic checkpoint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sato, M., Sekido, Y., Horio, Y., Takahashi, M., Saito, H., Minna, J. D., ... Hasegawa, Y. (2000). Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. Japanese Journal of Cancer Research, 91(5), 504-509.

Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. / Sato, Mitsuo; Sekido, Yoshitaka; Horio, Yoshitsugu; Takahashi, Masahide; Saito, Hidehiko; Minna, John D.; Shimokata, Kaoru; Hasegawa, Yoshinori.

In: Japanese Journal of Cancer Research, Vol. 91, No. 5, 05.2000, p. 504-509.

Research output: Contribution to journalArticle

Sato, M, Sekido, Y, Horio, Y, Takahashi, M, Saito, H, Minna, JD, Shimokata, K & Hasegawa, Y 2000, 'Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer', Japanese Journal of Cancer Research, vol. 91, no. 5, pp. 504-509.
Sato M, Sekido Y, Horio Y, Takahashi M, Saito H, Minna JD et al. Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. Japanese Journal of Cancer Research. 2000 May;91(5):504-509.
Sato, Mitsuo ; Sekido, Yoshitaka ; Horio, Yoshitsugu ; Takahashi, Masahide ; Saito, Hidehiko ; Minna, John D. ; Shimokata, Kaoru ; Hasegawa, Yoshinori. / Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. In: Japanese Journal of Cancer Research. 2000 ; Vol. 91, No. 5. pp. 504-509.
@article{8fb4e53f3b58418b9543ca12b262aefe,
title = "Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer",
abstract = "Mitotic checkpoint defects of the cell cycle have been implicated in the development of human cancers. Since hBUB1 and hBUBR1, whose products function in the spindle checkpoint pathway, have been shown to be mutated in a subset of colon cancers with chromosomal instability, we investigated the contribution of these genes to lung cancer development. One hundred and two lung cancer (50 small cell lung cancers and 52 non-small cell lung cancers) and 4 mesothelioma cell line DNAs were analyzed by Southern blot analysis, but no rearrangements or deletions of hBUB1 and hBUBR1 were detected. Using single strand conformation polymorphism analysis, we studied all the 25 exons except exon 1 of the hBUB1 gene in 88 lung cancer DNAs. One lung cancer cell line, NCI-H345, showed a single nucleotide substitution, which resulted in an Arg-to-Gln change at codon 209 (CGA to CAA). Eleven cell line DNAs exhibited a single nucleotide polymorphism in intron 9 of hBUB1, all of which were heterozygous. Similar mutation analysis of hBUBR1 in 47 lung cancer cell line cDNAs revealed a frequent polymorphism at codon 349 (CAA to CGA) leading to a substitution of Gln to Arg but no mutations. Northern blot analyses showed that both hBUB1 and hBUBR1 genes were expressed in all of 31 lung cancer cell lines tested with no significant difference in the expression level. Our results suggest that alterations in hBUB1 and hBUBR1 rarely contributed to the genetic change of lung cancers.",
keywords = "HBUB1, HBUBR1, Lung cancer, Mitotic checkpoint",
author = "Mitsuo Sato and Yoshitaka Sekido and Yoshitsugu Horio and Masahide Takahashi and Hidehiko Saito and Minna, {John D.} and Kaoru Shimokata and Yoshinori Hasegawa",
year = "2000",
month = "5",
language = "English (US)",
volume = "91",
pages = "504--509",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer

AU - Sato, Mitsuo

AU - Sekido, Yoshitaka

AU - Horio, Yoshitsugu

AU - Takahashi, Masahide

AU - Saito, Hidehiko

AU - Minna, John D.

AU - Shimokata, Kaoru

AU - Hasegawa, Yoshinori

PY - 2000/5

Y1 - 2000/5

N2 - Mitotic checkpoint defects of the cell cycle have been implicated in the development of human cancers. Since hBUB1 and hBUBR1, whose products function in the spindle checkpoint pathway, have been shown to be mutated in a subset of colon cancers with chromosomal instability, we investigated the contribution of these genes to lung cancer development. One hundred and two lung cancer (50 small cell lung cancers and 52 non-small cell lung cancers) and 4 mesothelioma cell line DNAs were analyzed by Southern blot analysis, but no rearrangements or deletions of hBUB1 and hBUBR1 were detected. Using single strand conformation polymorphism analysis, we studied all the 25 exons except exon 1 of the hBUB1 gene in 88 lung cancer DNAs. One lung cancer cell line, NCI-H345, showed a single nucleotide substitution, which resulted in an Arg-to-Gln change at codon 209 (CGA to CAA). Eleven cell line DNAs exhibited a single nucleotide polymorphism in intron 9 of hBUB1, all of which were heterozygous. Similar mutation analysis of hBUBR1 in 47 lung cancer cell line cDNAs revealed a frequent polymorphism at codon 349 (CAA to CGA) leading to a substitution of Gln to Arg but no mutations. Northern blot analyses showed that both hBUB1 and hBUBR1 genes were expressed in all of 31 lung cancer cell lines tested with no significant difference in the expression level. Our results suggest that alterations in hBUB1 and hBUBR1 rarely contributed to the genetic change of lung cancers.

AB - Mitotic checkpoint defects of the cell cycle have been implicated in the development of human cancers. Since hBUB1 and hBUBR1, whose products function in the spindle checkpoint pathway, have been shown to be mutated in a subset of colon cancers with chromosomal instability, we investigated the contribution of these genes to lung cancer development. One hundred and two lung cancer (50 small cell lung cancers and 52 non-small cell lung cancers) and 4 mesothelioma cell line DNAs were analyzed by Southern blot analysis, but no rearrangements or deletions of hBUB1 and hBUBR1 were detected. Using single strand conformation polymorphism analysis, we studied all the 25 exons except exon 1 of the hBUB1 gene in 88 lung cancer DNAs. One lung cancer cell line, NCI-H345, showed a single nucleotide substitution, which resulted in an Arg-to-Gln change at codon 209 (CGA to CAA). Eleven cell line DNAs exhibited a single nucleotide polymorphism in intron 9 of hBUB1, all of which were heterozygous. Similar mutation analysis of hBUBR1 in 47 lung cancer cell line cDNAs revealed a frequent polymorphism at codon 349 (CAA to CGA) leading to a substitution of Gln to Arg but no mutations. Northern blot analyses showed that both hBUB1 and hBUBR1 genes were expressed in all of 31 lung cancer cell lines tested with no significant difference in the expression level. Our results suggest that alterations in hBUB1 and hBUBR1 rarely contributed to the genetic change of lung cancers.

KW - HBUB1

KW - HBUBR1

KW - Lung cancer

KW - Mitotic checkpoint

UR - http://www.scopus.com/inward/record.url?scp=0034039988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034039988&partnerID=8YFLogxK

M3 - Article

C2 - 10835495

AN - SCOPUS:0034039988

VL - 91

SP - 504

EP - 509

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 5

ER -