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

Our plain-English summary of Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer, by M. Sato, Y. Sekido, Y. Horio, et al (Japanese Journal of Cancer Research, 2000).

The study

• Authors: M. Sato, Y. Sekido, Y. Horio, M. Takahashi, H. Saito, J.D. Minna, K. Shimokata, Y. Hasegawa
• Journal: Japanese Journal of Cancer Research
• Published: 2000;91(5):504-9
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory study of cancer cell lines, not of people. The article does not mention asbestos. The authors looked for changes in two genes, hBUB1 and hBUBR1, that help control how chromosomes are divided when a cell splits. They used 106 cell lines: 50 small cell lung cancers, 52 non-small cell lung cancers and 4 mesotheliomas. A test for large deletions or rearrangements of the two genes found none in any of these cell lines. The search for small changes covered lung cancer lines only. In hBUB1, among 88 lung cancer cell lines, one small cell line, NCI-H345, had a single-letter change at codon 209 that swapped one amino acid (Arg to Gln). The authors could not tell whether this was a mutation or a rare polymorphism. Eleven lines carried a polymorphism in intron 9. In hBUBR1, among 47 lung cancer cell lines, they found a frequent polymorphism at codon 349 but no mutations. Both genes were expressed in all 31 cell lines tested, including 2 mesotheliomas, with about a 4-fold range in levels. The authors concluded that alterations in these genes rarely contributed to lung cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of tumor cell lines (gene mutation and expression analysis using Southern blot, SSCP with sequencing, and northern blot)
• Who was studied: 106 tumor cell lines: 50 small cell lung cancers (SCLC), 52 non-small cell lung cancers (NSCLC) and 4 mesotheliomas. hBUB1 was screened for small changes in 88 lung cancer lines (46 SCLC, 42 NSCLC) and hBUBR1 in 47 lung cancer lines (24 SCLC, 23 NSCLC). Expression was tested in 31 lines (13 SCLC, 14 NSCLC, 2 unclassified lung cancers, 2 mesotheliomas).
• Main results:
  • Southern blot analysis of all 102 lung cancer and 4 mesothelioma cell lines found no rearrangements or deletions of hBUB1 or hBUBR1
  • In the SCLC cell line NCI-H345, hBUB1 had a single nucleotide substitution at codon 209 (CGA to CAA), changing Arg to Gln; it was the only such change among the 88 lung cancer lines screened
  • 11 of the 88 lung cancer cell lines (5 SCLCs and 6 NSCLCs) carried a heterozygous single nucleotide polymorphism in intron 9 of hBUB1
  • Among 47 lung cancer cell lines, hBUBR1 showed a frequent polymorphism at codon 349 (Gln to Arg): 24 lines expressed the Gln form, 14 the Arg form, and 9 both. The authors considered this a polymorphism, not a mutation.
  • One lung cancer line (H1304) had a change at hBUBR1 codon 952 that did not alter the amino acid
  • Both genes were expressed in all 31 cell lines tested, including 2 mesotheliomas, with about a 4-fold difference between the highest and lowest levels for each gene
• The authors' conclusion: The authors concluded that alterations in hBUB1 and hBUBR1 rarely contributed to the genetic changes of lung cancers. They said other parts of the spindle checkpoint machinery should be investigated.
• Limitations the authors state:
  • Normal (constitutional) DNA from the patient behind NCI-H345 was not available, so the authors could not tell whether the codon 209 change was a somatic mutation or a rare polymorphism
  • The codon 209 change might have no effect on the protein's function, because the mouse gene has Gln at that position
  • It is unclear whether the modest differences in expression levels matter for cancer development

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Colorectal Cancer, Small Cell Lung Cancer, Non-Small Cell Lung Cancer, Mesothelioma.

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