Mitochondrial genome instability in colorectal adenoma and adenocarcinoma

被引:22
作者
de Araujo, Luiza F. [1 ,2 ]
Fonseca, Aline S. [1 ,2 ]
Muys, Bruna R. [1 ,2 ]
Placa, Jessica R. [2 ]
Bueno, Rafaela B. L. [1 ,2 ]
Lorenzi, Julio C. C. [1 ,2 ]
Santos, Anemari R. D. [2 ]
Molfetta, Greice A. [1 ,2 ,3 ]
Zanette, Dalila L. [1 ,2 ,3 ]
Souza, Jorge E. S. [2 ,3 ]
Valente, Valeria [2 ,3 ,4 ]
Silva, Wilson A., Jr. [1 ,2 ,3 ]
机构
[1] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, BR-14049 Ribeirao Preto, Brazil
[2] CNPq, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ctr Cell Based Therapy CEPID FAPESP, Reg Blood Ctr Ribeirao Preto, Ribeirao Preto, Brazil
[3] Ctr Integrat Syst Biol CISBi NAP USP, Ctr Med Genom HCFMRP USP, Ribeirao Preto, Brazil
[4] Univ Sao Paulo State, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara, Brazil
基金
巴西圣保罗研究基金会;
关键词
Mitochondrial genome; Colorectal cancer; Heteroplasmy; Genome instability; DNA MUTATIONS; COMPLEX-I; METABOLISM; GENERATION; MTDNA; TUMORIGENESIS; PROGRESSION; FREQUENCY; SEQUENCE; CELLS;
D O I
10.1007/s13277-015-3640-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mitochondrial dysfunction is regarded as a hallmark of cancer progression. In the current study, we evaluated mitochondrial genome instability and copy number in colorectal cancer using Next Generation Sequencing approach and qPCR, respectively. The results revealed higher levels of heteroplasmy and depletion of the relative mtDNA copy number in colorectal adenocarcinoma. Adenocarcinoma samples also presented an increased number of mutations in nuclear genes encoding proteins which functions are related with mitochondria fusion, fission and localization. Moreover, we found a set of mitochondrial and nuclear genes, which cooperate in the same mitochondrial function simultaneously mutated in adenocarcinoma. In summary, these results support an important role for mitochondrial function and genomic instability in colorectal tumorigenesis.
引用
收藏
页码:8869 / 8879
页数:11
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