Involvement of activation-induced cytidine deaminase in skin cancer development

The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and Aging

“…Wong et al (2013) showed that exposure to chronic inflammation could drive invasive cutaneous carcinomas from diverse genetic and biological inciting events. Strikingly, SASP-like inflammation in the skin mediated by IL1β and transforming growth factor-β can drive the expression of activation-induced cytidine deaminase, which leads to squamous cell carcinomas (SCCs) carrying Hras and Trp53 mutations, independent of any exposure to UVR (Nonaka et al, 2016). Further, a recent study demonstrated that activation of oncogenic Hras in the mouse epidermis has differential effects in young and old skin.…”

Enhancing the efficacy of glycolytic blockade in cancer cellsviaRAD51 inhibition

“…As published previously, about half of all CLLs express AID, and a number of publications show the expression of AID in non-lymphoid tumors, presenting the possibility that this therapy could potentially be used for non-lymphoid cancers. 17,18,20,21,23 The observation that the combination of both glycolytic blockade and RAD51 inhibition leads to enhanced efficacy against tumorigenesis can be explained in two ways: First, ATP is required for multiple processes other than repair. Thus, reducing glycolysis by 2DG ( Figure 5E) weakens the cancer cell, regardless of the action of DIDS.…”

“…17,18 In addition, a number of studies have shown that non-B-cell malignancies also express this enzyme. [19][20][21][22][23] It has been hypothesized that the presence of AID assists in enhancing the generation of somatic mutations of the cancer genome, resulting in increased survival and/or propagation of the cancer. 18,22,24,25 We previously identified a small-molecule RAD51-specific inhibitor, 4,4ʹ-Diisothiocyano-2,2ʹ-stilbenedisulfonic acid (DIDS), that specifically disrupts the repair of AID-induced breaks in primary and neoplastic mouse B-cells and inhibits the growth of AID-positive human CLL cancers ex vivo.…”

Genomic basis for RNA alterations revealed by whole-genome analyses of 27 cancer types

“…Genome-wide, this identified 649 somatic eQTL (FDR ≤ 5%; Supplementary Table 4) associated with 567 unique regions. Among these, 11 somatic eQTL were explained by mutational burdens in exons or introns, including genes with known roles in the pathogenesis of specific cancers such as CDK12 in ovarian cancer 29,30 , PI4KA in hepatocellular carcinoma 31 , IRF4 in leukemia 32 , AICDA in skin melanoma 33 , C11orf73 in clear cell renal cancer 34 and BCL2 and SGK1 in lymphoma 35 , Extended Data Figure 12a-g). The majority of eGenes (68.4%) involved associations with flanking non-coding intervals (272 intergenic, 172 intronic regions, Figure 2d), and were due to mutations observed in multiple cancers (Extended Data Figure 13a, Supplementary Table 4).…”