In 1962, a particular extrachromosomal small body structure was observed and reported in the pleural effusion of lung cancer. Afterwards, these structures were named double minute chromosomes (DMs). As an extrachromosomal gene amplification marker, DMs are acentric, atelomeric, and self-replicating bodies existing in pairs, which usually carry oncogenes and drug resistance genes and are closely related with tumor progression and drug resistance.

Research summary

Our lab started the structure and function research of DMs in 1998 and we are the only lab doing the systematic biological research of DMs in China. From the ultrastructure to molecular structure and the function of related genes, we have done detailed analysis into the structure characteristics and sequence function of DMs,  disclosed the  mechanism of DMs’s formation, as well as explored the relationships between DMs and tumor drug resistance.

Research fields

1. Ultrastructure research of DMs.

2. Origination, sequence and structure analysis of DMs in different tumors.

3. Function study of genes carried by DMs and their related signal transduction pathways.

4. Mechanism study of DMs formation and development in the process of drug resistance in solid tumor.

Publications (*correspondence author)

1. Tian X, Liu C, Wang X, Wang F, Wang L, Xu L, Ma J, Gao Y, Bao Y, Wang F, Sun L, Wei J, Lin C, Zhang H, Zhu G, Guan X, Fu S, Zhang C*(2018)Sei-1 promotes double minute chromosomes formation through activation of the   PI3K/Akt/BRCA1-Abraxas pathway and induces double-strand breaks in NIH-3T3 fibroblasts. Cell Death Dis. 9(3): 341.

2. Yantao Bao, Jia Liu, Jia You, Di Wu, Yang Yu, Chang Liu, Lei Wang, Fei Wang, Lu Xu, Liqun Wang, Nan Wang, Xing Tian, Falin Wang, Hongbin Liang, Yating Gao, Xiaobo Cui, Guohua Ji, Jing Bai, Jingcui Yu, Xiangning Meng, Yan Jin, Wenjing Sun, Xin-yuan Guan, Chunyu Zhang*, Songbin Fu*. (2016)Met promotes the formation of double minute chromosomes induced by Sei-1 in NIH-3T3 murine fibroblasts. Oncotarget.7(35):56664-56675

3. Meng X, Qi X, Guo H, Cai M, Li C, Zhu J, Chen F, Guo H, Li J, Zhao Y, Liu P, Jia X, Yu J, Zhang C, Sun W, Yu Y, Jin Y, Bai J, Wang M,Rosales J, Lee KY, Fu S*.(2015)Novel role for non-homologous end joining in the formation of double minutes in methotrexate-resistant colon cancer cells. J Med Genet.52(2):135-44.

4. Sun W, Quan C, Huang Y, Ji W, Yu L, Li X, Zhang Y, Zheng Z, Zou H, Li Q, Xu P, Feng Y, Li L, Zhang Y, Cui Y, Jia X, Meng X, Zhang C, Jin Y, Bai J, Yu J, Yu Y,Yang J*, Fu S*. (2015)Constitutive ERK1/2 activation contributes to production of double minute chromosomes in tumour cells. J Pathol,2015;235(1):14-24.

5. Xu J, Liu P, Meng X, Bai J, Fu S, Guan R*, Sun W*. (2015)Association between sister chromatid exchange and double minute chromosomes in human tumor cells. Mol Cytogenet. 19;8:91.

6. Ji W, Bian Z, Yu Y, Yuan C, Liu Y, Yu L, Li C, Zhu J, Jia X, Guan R, Zhang C, Meng X, Jin Y, Bai J, Yu J, Lee KY, Sun W*, Fu S*. (2014)Expulsion of micronuclei containing amplified genes contributes to a decrease in double minute chromosomes from malignant tumor cells.Int J Cancer.134(6):1279-1288

7. Yu L, Zhao Yan, Quan C, Ji W, Zhu J, Huang Y, Guan R, Sun D, Jin Y, Meng X, Zhang C, Yu Y, Bai J, Sun W, and Fu S*.(2013)Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells. Plos One. 8(8):e71988.

8. Zhu J, Yu Y, Meng X, Fan Y, Zhang Y, Zhou C, Yue Z, Jin Y, Zhang C, Yu L, Ji W, Jia X, Guan R, Wu J, Yu J, Bai J, Guan XY, Wang M, Lee KY, Sun W, and Fu S*. (2013) De novo-generated small palindromes are characteristic of amplicon boundary junction of double minutes. Int J Cancer.133(4):797-806.

9. Jin Y, Liu Z, Cao W, Ma X, Fan Y, Yu Y, Bai J, Chen F, Rosales J, Lee KY, and Fu S*. (2012) Novel functional MAR elements of double minute chromosomes in human ovarian cells capable of enhancing gene expression. PLoS One. 7(2):e30419.

10. Fan Y, Mao R, Lv H, Xu J, Yan L, Liu Y, Shi M, Ji G, Yu Y, Bai J, Jin Y, and Fu S*. (2011) Frequency of double minute chromosomes and combined cytogenetic abnormalities and their characteristics. J Appl Genet. 52(1):53-9.

11. Kong F, Zhu J, Wu J, Peng J, Wang Y, Wang Q, Fu S, Yuan LL, and Li T. (2011) dbCRID: a database of chromosomal rearrangements in human diseases. Nucleic Acids Res. 39(Database issue):D895-900.

12. Fan Y, Mao R, Bai J, Zhang X, Lei Q, Fu S*. (2008) AFM images of G1-phase premature condensed chromosomes:Evidence for 30 nm changed to 50 nm chromatin fibers. Applied Surface Science. 254(6):1676-83.

13. Fan Y, Zhang X, Bai J, Mao R, Zhang C, Lei Q, Fu S*. (2007) Ultrastructural organization of premature condensed chromosomes at S-phase as observerd by atomic force microscopy. Applied Surface Science. 253(12):5281-6.

14. Zhang CY, Feng YX, Yu Y, Sun WJ, Bai J, Chen F, Fu SB*. (2006) The molecular mechanism of resistance to methotrexate in mouse methotrexate-resistant cells by cancer drug resistance and metabolism SuperArray. Basic Clin Pharmacol Toxicol. 99(2):141-5.

15. Deng X, Zhang L, Zhang Y, Yan Y, Xu Z, Dong S, and Fu S*. (2006) Double minute chromosomes in mouse methotrexate-resistant cells studied by atomic force microscopy. Biochem Biophys Res Commun, 346(4):1228-33.

16. Feng YX, Bai J, Zhang CY, Fu SB*. (2006) Proteomic analysis for the identification of proteins related to methotrexate resistance. Yi Chuan Xue Bao. 33(5):391-6.