Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity - PubMed (original) (raw)
Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity
D D Von Hoff et al. Proc Natl Acad Sci U S A. 1992.
Abstract
Oncogene amplification has been observed in a broad spectrum of human tumors and has been associated with a poor prognosis for patients with several different types of malignancies. Importantly, at biopsy, the amplified genes localize to acentric extrachromosomal elements such as double-minute chromosomes (DMs) in the vast majority of cases. We show here that treatment of several human tumor cell lines with low concentrations of hydroxyurea accelerates the loss of their extrachromosomally amplified oncogenes. The decreases in MYC copy number in a human tumor cell line correlated with a dramatic reduction in cloning efficiency in soft agar and tumorigenicity in nude mice. No effect on gene copy number or tumorigenicity was observed for a closely related cell line containing the same number of chromosomally amplified MYC genes. One step involved in the accelerated loss of extrachromosomal elements is shown to involve their preferential entrapment of DMs within micronuclei. The data suggest that agents that accelerate the loss of extrachromosomally amplified genes could provide valuable tools for moderating the growth of a large number of human neoplasms.
Similar articles
- Induction of differentiation in HL60 cells by the reduction of extrachromosomally amplified c-myc.
Eckhardt SG, Dai A, Davidson KK, Forseth BJ, Wahl GM, Von Hoff DD. Eckhardt SG, et al. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6674-8. doi: 10.1073/pnas.91.14.6674. Proc Natl Acad Sci U S A. 1994. PMID: 8022834 Free PMC article. - Hydroxyurea accelerates loss of extrachromosomally amplified genes from tumor cells.
Von Hoff DD, Waddelow T, Forseth B, Davidson K, Scott J, Wahl G. Von Hoff DD, et al. Cancer Res. 1991 Dec 1;51(23 Pt 1):6273-9. Cancer Res. 1991. PMID: 1682044 - Selective capture of acentric fragments by micronuclei provides a rapid method for purifying extrachromosomally amplified DNA.
Shimizu N, Kanda T, Wahl GM. Shimizu N, et al. Nat Genet. 1996 Jan;12(1):65-71. doi: 10.1038/ng0196-65. Nat Genet. 1996. PMID: 8528254 - Double minute chromosomes and homogeneously staining regions in tumors taken directly from patients versus in human tumor cell lines.
Benner SE, Wahl GM, Von Hoff DD. Benner SE, et al. Anticancer Drugs. 1991 Feb;2(1):11-25. doi: 10.1097/00001813-199102000-00002. Anticancer Drugs. 1991. PMID: 1720337 Review. - Molecular mechanisms of the origin of micronuclei from extrachromosomal elements.
Shimizu N. Shimizu N. Mutagenesis. 2011 Jan;26(1):119-23. doi: 10.1093/mutage/geq053. Mutagenesis. 2011. PMID: 21164192 Review.
Cited by
- CytoCellDB: a comprehensive resource for exploring extrachromosomal DNA in cancer cell lines.
Fessler J, Ting S, Yi H, Haase S, Chen J, Gulec S, Wang Y, Smyers N, Goble K, Cannon D, Mehta A, Ford C, Brunk E. Fessler J, et al. NAR Cancer. 2024 Aug 1;6(3):zcae035. doi: 10.1093/narcan/zcae035. eCollection 2024 Sep. NAR Cancer. 2024. PMID: 39091515 Free PMC article. - Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.
Meng XN, Ma JF, Liu YH, Li SQ, Wang X, Zhu J, Cai MD, Zhang HS, Song T, Xing S, Hou LQ, Guo H, Cui XB, Han J, Liu P, Ji GH, Sun WJ, Yu JC, Fu SB. Meng XN, et al. Br J Cancer. 2024 May;130(11):1819-1827. doi: 10.1038/s41416-024-02664-0. Epub 2024 Apr 9. Br J Cancer. 2024. PMID: 38594370 Free PMC article. - Insight on ecDNA-mediated tumorigenesis and drug resistance.
Huang Q, Zhang S, Wang G, Han J. Huang Q, et al. Heliyon. 2024 Mar 11;10(6):e27733. doi: 10.1016/j.heliyon.2024.e27733. eCollection 2024 Mar 30. Heliyon. 2024. PMID: 38545177 Free PMC article. Review. - Acquired Cross-Resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC Paralogs.
Pal Choudhuri S, Girard L, Lim JYS, Wise JF, Freitas B, Yang D, Wong E, Hamilton S, Chien VD, Kim YJ, Gilbreath C, Zhong J, Phat S, Myers DT, Christensen CL, Mazloom-Farsibaf H, Stanzione M, Wong KK, Hung YP, Farago AF, Meador CB, Dyson NJ, Lawrence MS, Wu S, Drapkin BJ. Pal Choudhuri S, et al. Cancer Discov. 2024 May 1;14(5):804-827. doi: 10.1158/2159-8290.CD-23-0656. Cancer Discov. 2024. PMID: 38386926 Free PMC article. - Novel insights into the ecDNA formation mechanism involving MSH3 in methotrexate‑resistant human colorectal cancer cells.
Wang X, Qu Y, Xing R, Zhou J, Liu Y, Zhang H, Zhu J, Ma J, Cui X, Song T, Xing S, Ji G, Liu P, Sun W, Fu S, Meng X. Wang X, et al. Int J Oncol. 2023 Dec;63(6):134. doi: 10.3892/ijo.2023.5582. Epub 2023 Oct 27. Int J Oncol. 2023. PMID: 37888748 Free PMC article.
References
- Nature. 1977 Nov 24;270(5635):347-9 - PubMed
- Cancer Res. 1979 Dec;39(12):4914-24 - PubMed
- Hereditas. 1977;86(1):75-90 - PubMed
- Cancer Res. 1991 Dec 1;51(23 Pt 1):6273-9 - PubMed
- Anticancer Drugs. 1991 Feb;2(1):11-25 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources