Research Papers:

Error-prone DNA polymerase and oxidative stress increase the incidences of A to G mutations in tumors

Jiannan Lin and Tieliu Shi _

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Oncotarget. 2017; 8:45154-45163. https://doi.org/10.18632/oncotarget.13293

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Jiannan Lin1 and Tieliu Shi1

1The Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China

Correspondence to:

Tieliu Shi, email: [email protected]

Keywords: A to G mutation, mutational mechanism, error-prone DNA polymerase, oxidative stress, RAS mutation

Received: August 29, 2016     Accepted: October 29, 2016     Published: November 11, 2016


Mutational processes for A→G mutations in tumors are not well understood. To uncover the mutational mechanisms, we analyzed molecular profiles of more than 9,000 tumor samples from The Cancer Genome Atlas (TCGA). The present study found that error-prone DNA polymerases were involved in stomach tumors with high fraction of A→G mutations. High levels of apoptosis in kidney cancers and high levels of energy metabolism in thyroid cancers increased A→G mutation rate, which was associated with high oxidative stress. We also found that the frequencies of RAS gene mutations were increased in thyroid cancers with high level of energy metabolism because of high-frequency A→G mutations.

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