Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer

R G Jaffrey, S C Pritchard, C Clark, G I Murray, J Cassidy, K M Kerr, M C Nicolson, H L McLeod

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Genomic instability is observed in the majority of human tumors. Dysregulation of the mitotic spindle checkpoint is thought to be one of the mechanisms that facilitate aneuploidy in tumor cells. Mutations in the mitotic spindle checkpoint kinase BUB1 cause a dominant negative disruption of the spindle, leading to chromosome instability in cancer cell lines. However, little is known about chromosome 2q14, the genomic region containing BUB1, in human tumors. The BUB1 locus mas evaluated in 32 colorectal cancer (CRC) and 20 non-small cell lung cancer (NSCLC) primary tumors using a panel of seven microsatellite repeats for 2q, two CA repeats in BUB1, and gene mutation analysis, The 2q locus mas allelically stable in NSCLC but relatively unstable in colorectal primary tumors (20 of 32 tumors, 62.5%). In addition, 14.5% of CRC patients displayed instability within BUB1. Previously described BUB1 mutations and polymorphisms were rare (<1%) in the CRC or NSCLC tumors. Our data demonstrate 2q and BUB1 allelic instability in CRC and indicate that mutations in BUB1 are rare causes of chromosome instability in CRC or NSCLC, Additional investigations may shed light on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal tumor initiation and progression.

Original languageEnglish
Pages (from-to)4349-4352
Number of pages4
JournalCancer Research
Volume60
Publication statusPublished - 2000

Keywords

  • MITOTIC CHECKPOINT GENES
  • CHROMOSOMAL INSTABILITY
  • SPINDLE CHECKPOINT
  • IN-VIVO
  • CARCINOMA
  • TUMORS
  • HSMAD2
  • HBUB1
  • MAP

Cite this

Jaffrey, R. G., Pritchard, S. C., Clark, C., Murray, G. I., Cassidy, J., Kerr, K. M., ... McLeod, H. L. (2000). Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer. Cancer Research, 60, 4349-4352.

Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer. / Jaffrey, R G ; Pritchard, S C ; Clark, C ; Murray, G I ; Cassidy, J ; Kerr, K M ; Nicolson, M C ; McLeod, H L .

In: Cancer Research, Vol. 60, 2000, p. 4349-4352.

Research output: Contribution to journalArticle

Jaffrey, RG, Pritchard, SC, Clark, C, Murray, GI, Cassidy, J, Kerr, KM, Nicolson, MC & McLeod, HL 2000, 'Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer', Cancer Research, vol. 60, pp. 4349-4352.
Jaffrey RG, Pritchard SC, Clark C, Murray GI, Cassidy J, Kerr KM et al. Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer. Cancer Research. 2000;60:4349-4352.
Jaffrey, R G ; Pritchard, S C ; Clark, C ; Murray, G I ; Cassidy, J ; Kerr, K M ; Nicolson, M C ; McLeod, H L . / Genomic instability at the BUB1 locus in colorectal cancer, but not in non-small cell lung cancer. In: Cancer Research. 2000 ; Vol. 60. pp. 4349-4352.
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AU - Nicolson, M C

AU - McLeod, H L

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N2 - Genomic instability is observed in the majority of human tumors. Dysregulation of the mitotic spindle checkpoint is thought to be one of the mechanisms that facilitate aneuploidy in tumor cells. Mutations in the mitotic spindle checkpoint kinase BUB1 cause a dominant negative disruption of the spindle, leading to chromosome instability in cancer cell lines. However, little is known about chromosome 2q14, the genomic region containing BUB1, in human tumors. The BUB1 locus mas evaluated in 32 colorectal cancer (CRC) and 20 non-small cell lung cancer (NSCLC) primary tumors using a panel of seven microsatellite repeats for 2q, two CA repeats in BUB1, and gene mutation analysis, The 2q locus mas allelically stable in NSCLC but relatively unstable in colorectal primary tumors (20 of 32 tumors, 62.5%). In addition, 14.5% of CRC patients displayed instability within BUB1. Previously described BUB1 mutations and polymorphisms were rare (<1%) in the CRC or NSCLC tumors. Our data demonstrate 2q and BUB1 allelic instability in CRC and indicate that mutations in BUB1 are rare causes of chromosome instability in CRC or NSCLC, Additional investigations may shed light on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal tumor initiation and progression.

AB - Genomic instability is observed in the majority of human tumors. Dysregulation of the mitotic spindle checkpoint is thought to be one of the mechanisms that facilitate aneuploidy in tumor cells. Mutations in the mitotic spindle checkpoint kinase BUB1 cause a dominant negative disruption of the spindle, leading to chromosome instability in cancer cell lines. However, little is known about chromosome 2q14, the genomic region containing BUB1, in human tumors. The BUB1 locus mas evaluated in 32 colorectal cancer (CRC) and 20 non-small cell lung cancer (NSCLC) primary tumors using a panel of seven microsatellite repeats for 2q, two CA repeats in BUB1, and gene mutation analysis, The 2q locus mas allelically stable in NSCLC but relatively unstable in colorectal primary tumors (20 of 32 tumors, 62.5%). In addition, 14.5% of CRC patients displayed instability within BUB1. Previously described BUB1 mutations and polymorphisms were rare (<1%) in the CRC or NSCLC tumors. Our data demonstrate 2q and BUB1 allelic instability in CRC and indicate that mutations in BUB1 are rare causes of chromosome instability in CRC or NSCLC, Additional investigations may shed light on the mechanistic impact of the mitotic spindle checkpoint pathway in colorectal tumor initiation and progression.

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