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Personalized Medicine in Lung Cancer
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
Daniela Morales-Espinosa, Silvia Garcá-Román, Rafael Rosell
Excision repair cross-complementing group 1 (ERCC1) has a crucial role in nucleotide excision repair (NER) pathway, which is one of DDR machinery. So far, many studies have suggested that ERCC1 at the level of protein, messenger RNA, or germline DNA could be a prognostic or predictive biomarker in NSCLC patients treated with platinum doublets, though contradictory results have also been reported.18 A recent report in The New England Journal of Medicine by Friboulet and colleagues addressed the elegant validation of ERCC1 protein expression as a biomarker for adjuvant platinum-based chemotherapy and provided insights into the methodology to assess it.19 Further trials have been performed to validate the predictive or prognostic effect of ERCC1.20 Nevertheless, in these studies the discordance of ERCC1 H score between old and new batches of the 8F1 antibody and the point that four ERCC1 protein isoforms were heterogeneously expressed by alternative splicing in tumor samples with different functions in repairing platinum-DNA adduct, meant that no conclusive results could be extracted. Therefore the development of a specific antibody for functional isoform (ERCC1-202) will be necessary to more accurately predict the benefit from platinum.18
Pharmacogenomics of Colorectal Cancer
Published in Jim Cassidy, Patrick Johnston, Eric Van Cutsem, Colorectal Cancer, 2006
Patrick Johnston, Howard L. McLeod
Excision repair cross complementing 1 (ERCC1) is a highly conserved protein and is an essential member of the NER pathway (100). The ERCC1-XPF complex is involved in the cleavage of damaged DNA 5′ to the DNA lesion. It has been shown that low ERCC1 gene expression levels have correlated with improved overall survival after 5-FU/oxaliplatin therapy in patients with advanced colorectal cancer refractory to first-line chemotherapy (101). Furthermore, an independent study has demonstrated that both low TS and low ERCC1 mRNA expressions are associated with significantly improved survival in patients treated with 5FU/oxaliplatin (101).
Biomarkers of Toxicant Susceptibility
Published in Anthony P. DeCaprio, Toxicologic Biomarkers, 2006
XPD/ERCC2 (excision repair cross-complementing) is involved in the NER pathway (29), which recognizes and repairs a wide range of structurally unrelated lesions such as bulky adducts and thymidine dimers. The XPD protein is an evolutionarily conserved helicase, a subunit of transcription factor IIH (TFIIH), that is essential for transcription and NER. Recently, the entire coding region of the DNA repair gene XPD/ERCC2 was resequenced in 12 normal individuals, and six polymorphic variants were described (30). Rare XPD mutations, which prevent interaction with p44, another subunit of TFIIH, and reduce its helicase activity result in three distinct clinical genetic diseases: XP, trichothiodystrophy, and XP combined with Cockayne sydrome. The functional significance of these newly identified XPD variants is not known. Many XPD polymorphisms are identified, e.g., C22541A at codon 156 of exon 6, at codon 199 (Ile→Met), at codon 312 (Asp→Asn), and A35931C at codon 751 of exon 23 (Lys→Gln). Allele frequencies are higher than 25% in sample populations from North America, England, and Italy, but homozygous alleles are very rare. XPD-Lys751Gln polymorphism, a conservative substitution, is associated with reduced in vitro repair of X-ray-induced DNA damage.
Posterior subcapsular cataracts are a late effect after acute exposure to 0.5 Gy ionizing radiation in mice
Published in International Journal of Radiation Biology, 2021
Sarah Kunze, Alexander Cecil, Cornelia Prehn, Gabriele Möller, Andreas Ohlmann, Gerhild Wildner, Stephan Thurau, Kristian Unger, Ute Rößler, Sabine M. Hölter, Soile Tapio, Florian Wagner, Andreas Beyerlein, Fabian Theis, Horst Zitzelsberger, Ulrike Kulka, Jerzy Adamski, Jochen Graw, Claudia Dalke
All samples examined for this report were taken from the mice of a lifetime study that was described recently (Dalke et al. 2018). In brief, mice (wild-type and heterozygous Ercc2 mutant (Ercc2+/S737P) mice, both on B6C3F1 (F1 hybrids of C57BL/6J females and C3HeB/FeJ males) strain background; gene symbol Ercc2 means excision repair cross-complementing rodent repair deficiency, complementation group 2) were whole body gamma irradiated at the age of 10 weeks under a 60Co source (Eldorado 78 Teletherapy irradiator, AECL, Chalk River, Canada) by various doses (0, 0.063, 0.125, or 0.5 Gy at 0.063 Gy/min). Prior to each irradiation, the distance of the radiation source to the mice was adjusted, in order to ensure a dose rate of 0.063 Gy/min, monitored by a UNIDOS II dosimeter (secondary electrometer, calibration was based on the primary standards of the Physikalische-Technische Bundesanstalt-Braunschweig, Germany). Mice were irradiated at room temperature with the mice sitting in a plexiglass cylinder with a lid to avoid rearing of the mice. Supplementary Figure S1 gives an overview of the irradiation scheme. The mice were followed up to 24 months and samples were taken at different time points (4 and 24 h, 12, 18, and 24 months after irradiation) as indicated below. The study was approved by the Government of Upper Bavaria (Az. 55.2-1-54-2532-161-12). The use of animals was in strict accordance with the German Law of Animal Protection and the tenets of the Declaration of Helsinki.
Association of XRCC1 and XPD functional gene variants with nicotine dependence and/or schizophrenia: a case-control study and in silico analysis
Published in Psychiatry and Clinical Psychopharmacology, 2019
S. Pehlivan, N. Aydin, A. F. Nursal, M. A. Uysal, M. Pehlivan, A. Tekcan, F. K. Yavuz, U. Sever, H. Yavuzlar, S. Kurnaz, S. Uysal, P. C. Aydin
X-ray repair cross-complementing group 1 (XRCC1) gene, found at chromosome 19q13.2, is a major component of base excision repair (BER) and is necessary for genetic stability [6]. Xeroderma pigmentosum complementation group D (XPD) is among the crucial DNA repair genes [7]. This is also called as the excision repair cross-complementing complementation group 2 (ERCC2) gene and located in chromosome 19q13.2–13.3 and codes for an evolutionally conserved helicase which plays a key role in transcription and nucleotide excision repair (NER) [7]. Genetic variation in DNA repair genes can have an impact on the activity of DNA repair enzymes, thus modifying the DNA repair ability. This study aimed to find out whether functional SNP variants in the XRCC1 Arg399Gln (rs25487), XPD Lys751Gln (rs13181) variants play any role in both ND and Sch + ND etiopathogenesis in a Turkish population, which was followed up with an in silico analysis approach.
Genetics of endometriosis: a comprehensive review
Published in Gynecological Endocrinology, 2019
Danilo Deiana, Stefano Gessa, Michela Anardu, Angelos Daniilidis, Luigi Nappi, Maurizio N. D’Alterio, Alessandro Pontis, Stefano Angioni
Many studies have suggested that oxidative stress is involved in the physiopathology of endometriosis [37]. Reactive oxygen species’ excess DNA damage (e.g. base substitution) could explain the metaplastic nature of the disease. X-ray repair cross-complementing (XRCC)1, XRCC3 and excision repair cross-complementing (ERCC) each play a role in the DNA reparation system. Their malfunction contributes to the development of endometriosic lesions. In 2010, Attar et al. showed no significant difference in the frequencies of the genotype and polymorphic alleles of genes APE1 (Apurinic/Apyrimidinic Endonuclease 1), XRCC1, ERCC, XPG (Xeroderma Pigmentosus gene), and HOGG1 (8-Oxoguanine DNA Glycosylase 1). An increased risk seems to be associated with genotype Thr/Thr [38].