Abstract
Although APE2 plays essential roles in base excision repair and ATR-Chk1 DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. Here, we report multiple-cancer analyses of APE2 genomic alterations and mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We observe that APE2 genomic alterations occur at ~17% frequency in 14 cancer types (n = 21,769). Most frequent somatic mutations of APE2 appear in uterus (2.89%) and skin (2.47%) tumor samples. Furthermore, APE2 expression is upregulated in tumor tissue compared with matched non-malignant tissue across 5 cancer types including kidney, breast, lung, liver, and uterine cancers, but not in prostate cancer. We also examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. We show that APE2 mRNA expression is positively correlated with PCNA, APE1, XRCC1, PARP1, Chk1, and Chk2 across these 6 tumor tissue types; however, groupings of other DNA repair and DDR genes are correlated with APE2 with different patterns in different cancer types. Taken together, this study demonstrates alterations and abnormal expression of APE2 from multiple cancers.
Highlights
APE2 plays essential roles in base excision repair and ATR-Chk[1] DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients
Frequency of somatic mutations in APE2 ranged from 2.89% to 0.10%, its somatic mutations did not appear in kidney nor pancreas tumor tissue
The understanding of APE2 in DNA repair and DDR pathways has been derived from studies of model organisms such as Xenopus and yeast[9,10,11,45,46,47,48,49], despite some biochemical and sub-cellular localization characterization of human APE2 protein[28,50,51]
Summary
APE2 plays essential roles in base excision repair and ATR-Chk[1] DNA damage response (DDR) pathways, it remains unknown how the APE2 gene is altered in the human genome and whether APE2 is differentially expressed in cancer patients. We examine the mRNA expression of 13 other DNA repair and DDR genes from matched samples for 6 cancer types. SSBs and DNA replication stress trigger the activation of ATM and Rad3-related (ATR)- Checkpoint kinase 1 (Chk1) DDR pathway[9,10,11]. Nucleotide excision repair (NER) protein XPC may regulate OGG1 expression and participates in BER pathway to repair oxidative DNA damage, suggesting crosstalk between different DNA repair pathways[23,24]
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