The proliferation of tumor cells is an extremely energy-consuming process. However, different from normal cells, tumor cells generate energy via glycolysis even under aerobic conditions, which is one of the ten hallmarks of tumor cells. The switch of energy metabolism results in a series of physiological changes in tumor cells, including rapid generation of ATP and abundant biomass for cell proliferation, which form the basis of tumor cells to successfully adapt to their extreme microenvironment. In this thesis, we will introduce recent progress in studying somatic mutations on energy metabolism related genes in tumor, specially focus on the potential factors involving in the “switch” to shed a light on deciphering the genetic mechanisms underlying the “switch” of tumor cells. In accordance with the hypothesis that cancer formation is a process of somatic evolution driven by natural selection, signature of positive selection has been detected on a number of cancer-related genes. Considering mitochondrion is the “energy plant” of cells and the tumor cells need abundant ATP for proliferation. However, it is still controversial whether a similar selective pressure is also acting on mitochondrial DNA (mtDNA), small molecules in mitochondrion but has been suggested to play an important role in tumorigenesis by altering oxidative phosphorylation. To better understand the mutational pattern on cancerous mtDNA and decipher the genetic signature left by natural selection, a total of 186 entire mitochondrial genomes of cancerous and adjacent normal tissues from 93 esophageal cancer patients were obtained and extensively studied. Our results revealed that the observed mutational pattern on the cancerous mtDNAs might be best explained as relaxation of negative selection. Taken into account additional 1,235 cancerous (nearly) complete mtDNA sequences retrieved from literature, our results suggested that the relaxed selective pressure was the most likely explanation for the accumulation of mtDNA variation in different types of cancer.
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