Differences in the rates of gene amplification in nontumorigenic and tumorigenic cell lines as measured by Luria-Delbrück fluctuation analysis - PubMed (original) (raw)

Differences in the rates of gene amplification in nontumorigenic and tumorigenic cell lines as measured by Luria-Delbrück fluctuation analysis

T D Tlsty et al. Proc Natl Acad Sci U S A. 1989 Dec.

Abstract

It has been hypothesized that genomic fluidity is an important component of tumorigenesis. Previous studies described the relationship between tumorigenicity and one marker for genomic fluidity, gene amplification. In this report, these studies are extended with the rat liver epithelial cell lines to show that: (i) the amplification in these cells arises in a spontaneous fashion in the population (i.e., the variants detected are not preexisting in the population), and (ii) the rate of spontaneous amplification (mutation), as measured by Luria-Delbrück fluctuation analysis, is significantly lower in the nontumorigenic cells than in the tumorigenic cells. The rate was estimated by using the Po method and the method of means. The rate of spontaneous amplification of the gene encoding the multifunctional protein CAD (containing the enzymatic activities carbamoyl-phosphate synthase, aspartate transcarbamylase, and dihydroorotase) in the highly tumorigenic cells was significantly greater than that for the nontumorigenic cells, reaching almost 1 x 10(-4) events per cell per generation. The rate of this mutagenic event is high compared to the rate of point mutations usually reported in mammalian cells, and its potential contribution to the tumorigenic process will be discussed.

PubMed Disclaimer

Cited by

Prognostic and Immunotherapeutic Predictive Value of CAD Gene in Hepatocellular Carcinoma: Integrated Bioinformatics and Experimental Analysis.
Wang X, Feng JK, Mao FF, Hou YC, Zhang YQ, Liu LH, Wei Q, Sun JX, Liu C, Shi J, Cheng SQ. Wang X, et al. Mol Biotechnol. 2024 Apr 29. doi: 10.1007/s12033-024-01125-6. Online ahead of print. Mol Biotechnol. 2024. PMID: 38683442
Sequential mutations in exponentially growing populations.
Nicholson MD, Cheek D, Antal T. Nicholson MD, et al. PLoS Comput Biol. 2023 Jul 10;19(7):e1011289. doi: 10.1371/journal.pcbi.1011289. eCollection 2023 Jul. PLoS Comput Biol. 2023. PMID: 37428805 Free PMC article.
Ligand-Independent Actions of the Vitamin D Receptor: More Questions Than Answers.
Bikle DD. Bikle DD. JBMR Plus. 2021 Nov 23;5(12):e10578. doi: 10.1002/jbm4.10578. eCollection 2021 Dec. JBMR Plus. 2021. PMID: 34950833 Free PMC article. Review.
Serine hydroxymethyltransferase 2 expression promotes tumorigenesis in rhabdomyosarcoma with 12q13-q14 amplification.
Nguyen TH, Vemu PL, Hoy GE, Boudjadi S, Chatterjee B, Shern JF, Khan J, Sun W, Barr FG. Nguyen TH, et al. J Clin Invest. 2021 Aug 2;131(15):e138022. doi: 10.1172/JCI138022. J Clin Invest. 2021. PMID: 34166228 Free PMC article.
Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors.
Shaffer SM, Emert BL, Reyes Hueros RA, Cote C, Harmange G, Schaff DL, Sizemore AE, Gupte R, Torre E, Singh A, Bassett DS, Raj A. Shaffer SM, et al. Cell. 2020 Aug 20;182(4):947-959.e17. doi: 10.1016/j.cell.2020.07.003. Epub 2020 Jul 30. Cell. 2020. PMID: 32735851 Free PMC article.

References

1. Mutat Res. 1983 Oct;111(2):253-62 - PubMed
1. J Biol Chem. 1979 Sep 10;254(17):8679-89 - PubMed
1. Cancer Res. 1988 Mar 1;48(5):1060-5 - PubMed
1. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6949-52 - PubMed
1. Cell. 1984 Jul;37(3):705-13 - PubMed

Differences in the rates of gene amplification in nontumorigenic and tumorigenic cell lines as measured by Luria-Delbrück fluctuation analysis - PubMed (original) (raw)