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Xeroderma Pigmentosum
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
As the most important repair pathway in mammals for removal of UV light-induced lesions (including cyclobutane pyrimidine dimers [CPD], 6–4 photoproducts, and helix-distorting chemical adducts), the NER pathway consists of two subpathways, i.e., global genome repair (GGR) and transcription-coupled repair (TCR). The GGR subpathway is a slow process that utilizes XPC and DDB2/XPE to identify/mark DNA injuries/lesions anywhere in the genome. The TCR subpathway relies on CSA/ERCC8 and CSB/ERCC6 to detect DNA damages occurring at transcribed strands of active genes that block RNA polymerase II transcription/elongation and that are inefficiently recognized by the GGR subpathway, allowing rapid resumption of the vital process of RNA synthesis. Once detected, the DNA lesions are removed and repaired by the multi-subunit TFIIH complex (transcription factor II H complex, consisting of XPA, ERCC3/XPB, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, and other molecules) in the NER pathway. Specifically, XPB and XPD helicases in the TFIIH complex open the DNA double helix around the lesion, and XPA and replication protein A (RPA) help assemble and properly orientate XPF and XPG endonucleases, which excise the damaged strand around the lesion (5′ and 3′, respectively), leaving an excised stretch of ∼30 nucleotides for DNA polymerase δ/ε and auxiliary factors to fill, and ligase 1 to seal (Figure 50.1) [1,3,7].
Principles of Clinical Diagnosis
Published in Susan Bayliss Mallory, Alanna Bree, Peggy Chern, Illustrated Manual of Pediatric Dermatology, 2005
Susan Bayliss Mallory, Alanna Bree, Peggy Chern
Group D: skin cancer, CNS disorders; may have Cockayne syndrome or trichothiodystrophy; gene locus/gene: 19q13.2-q13.3/ ERCC2, EM9 Group E: few skin cancers, excision repair 40–50% of normal, gene locus: 11p12-p11Group F: mild skin symptoms, excision repair 10–20% of normal; gene locus: 16p13.3-p13.13; gene: ERCC4
Head and Neck Cancers
Published in Peter G. Shields, Cancer Risk Assessment, 2005
Qingyi Wei, Hongbing Shen, Margaret R. Spitz, Erich M. Sturgis, Peter G. Shields
Polymorphisms of DNA repair genes may also contribute to variations in DRC. Clearly, functional (phenotypic) studies of DNA repair in individuals with various DNA repair genotypes are needed. However, it will be difficult to detect subtle differences in DRC in such studies due to a single polymorphism of a single gene in a very complex pathway. Recently, the entire coding regions of the following DNA repair genes on chromosome 19 were resequenced in 12 normal individuals (132): three NER genes (ERCC1, XPD/ERCC2, and XPF/ERCC4), one HRR gene (XRCC3), and one BER gene (XRCC1). Among these, 7 variants of ERCC1, 17 variants of XPD/ERCC2, 6 variants of XPF/ERCC4, 4 variants of XRCC3, and 12 variants of XRCC1 were identified. Of these variants, 4 of XPD/ERCC2,3of XRCC1,1of XRCC3 and 1 of XPF/ERCC4 result in an amino acid sequence change. Later, another 6 variants of XPF/ERCC4 were identified in 38 individuals (133), 2 variants of XPA (chromosome 9), and 2 variants of XPB/ERCC3 (chromosome 2) were identified in 35 individuals, and 2 variants of XPC (chromosome 3) (134) and 3 variants of XPG/ERCC5 (chromosome 13) (135) were also identified. Although the significance of these variants is largely unknown, the implication is those that cause amino acid substitutions may have an impact on the function of the proteins and therefore on the efficiency of DNA repair. Variants that do not cause an amino acid change may also have an impact on the DNA repair function through altered splicing, mRNA instability, or linkage with other genetic changes. Therefore, knowing the impact of these polymorphisms on disease risk is important to ultimately understanding their functional relevance.
Analysis and clinical characteristics of acute myeloid leukemia developing with prior or concurrent tumors in non cyto- or radiotherapy exposure patients in a single center
Published in Hematology, 2023
Yu Lian, Juanjuan Ti, Liangming Ma, Jia Wei, Zhilin Gao
Notably, a patient was diagnosed with diffuse large B-cell lymphoma (DLBCL) six years after receiving chemotherapy for AML. The incidence of tMN following radio- or chemotherapy for lymphoma has been reported as 0.8-6.3% at 20 years, but secondary non-Hodgkin lymphoma with prior AML is quite rare and has only been reported in a few cases [12,13]. Therefore, we performed whole exome sequencing in tumor tissues and non-carcinoma adjacent tissues. We identified several germline mutations and selected cancer-predisposing genes via the Cancer Gene Census database (http://cancer.sanger.ac.uk/cancergenome/projects/census/). Mutations in CBLB, HOXC13, PTPRC, ERCC4, TSC1, SETBP1, and AHCTF1 were included: mutations in CBLB, HOXC13, and SETBP1 were more predisposed to AML; mutation of PTPRC was predisposed to T-ALL; and mutations of ERCC4 and TSC1 were predisposed to cancer of skin cells or renal and bladder cells, respectively.
Bioinformatics analysis deciphering the transcriptomic signatures associated with signalling pathways and prognosis in the myelodysplastic syndromes
Published in Hematology, 2022
Niluopaer Tuerxun, Jie Wang, Fang Zhao, Yu-ting Qin, Huan Wang, Rong Chen, Jian-ping Hao
We speculate that the prognostic sixteen hub genes (MX2, GBP2, PXN, IFI44, FDXR, PLCB2, ASS1, ERCC4, PML, RRAGD, CD19, PAX5, TCF3, LEF1, NUSAP1, and TIMELESS) have diagnostic value in MDS patients. We used the GSE58831 dataset (n = 176) to validate our hypothesis, and the results showed that the ROC curve of the expression levels of MX2, GBP2, PXN, IFI44, FDXR, PLCB2, ASS1, ERCC4, PML, RRAGD, CD19, PAX5, TCF3, LEF1, NUSAP1, and TIMELESS hub genes showed excellent diagnostic value for MDS patients (n = 159) when compared with normal samples (n = 17) (Figure 8). The cut-off points, AUC, 95% CI, sensitivity, specificity, PPV, and NPV of these16 genes are illustrated in Table 5. The value of area under the ROC curve (AUC) of PXN, FDXR, PLCB2, PML, CD19, PAX5, and LEF1 genes are more than 0.80, indicating that these genes could be effectively used for diagnostic efficacy in the MDS.
Incorporating molecular biomarkers into clinical practice for gastric cancer
Published in Expert Review of Anticancer Therapy, 2019
Shunsuke Nakamura, Mitsuro Kanda, Yasuhiro Kodera
Xie et al [78] . analyzed the expression and function of MiR-192-5p in the nucleotide excision repair (NER) pathway and its role in resistance of GC to cisplatin. Comet assays revealed that the ability of SGC7901/DDP (SCG7901 cisplatin resistant cells) to repair DNA damage is significantly higher compared with that of SGC7901 cells and positively correlates with resistance to cisplatin. The levels of the NER proteins ERCC excision repair 3 (ERCC3) and ERCC4 positively correlate with resistance to cisplatin of SGC7901/DDP cells. Further, analysis of miRNA arrays shows that the levels of MiR-192-5p are significantly lower in SGC7901/DDP cells compared with those of SGC7901 cells. Moreover, upregulation of MiR-192-5p synthesis reverses the resistance of SGC7901/DDP cells to cisplatin by inhibiting the expression of ERCC3 and ERCC4 in vitro and vivo, suggesting that ERCC3 and ERCC4 are targets of MiR-192-5p in these cells [78]. Thus, MiR-192-5p may serve as a potential biomarker and therapeutic target of GC resistance to cisplatin.