• ABCB1
• ABCG2
• Gallbladder cancer
• Immunohistochemistry
• Methylation-specific PCR
• Real-time PCR

• Humans
• Female
• Middle Aged
• Gallbladder Neoplasms/genetics
• ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics
• ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism
• Clinical Relevance
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• ATP-Binding Cassette Transporters/genetics
• ATP-Binding Cassette Transporters/metabolism
• RNA, Messenger/genetics
• Drug Resistance, Neoplasm/genetics
• ATP Binding Cassette Transporter, Subfamily B/genetics

• ABCG2
• Angiogenesis
• Cancer stem cells
• Curcumin
• HUVECs
• Quinacrine

• cervical cancer
• cisplatin
• ercc1
• mechanism
• survival

The resistance of tumor cells to therapy severely impairs the efficacy of treatment, leading to recurrence and metastasis of various cancers. Clarifying the underlying mechanisms of therapeutic resistance may provide new strategies for overcoming cancer resistance. N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotes, and is involved in the regulation of RNA splicing, translation, transport, degradation, stability and processing, thus affecting several physiological processes and cancer progression. As a novel type of multifunctional non-coding RNAs (ncRNAs), circular RNAs (circRNAs) have been demonstrated to play vital roles in anticancer therapy. Currently, accumulating studies have revealed the mutual regulation of m6A modification and circRNAs, and their interaction can further influence the sensitivity of cancer treatment. In this review, we mainly summarized the recent advances of m6A modification and circRNAs in the modulation of cancer therapeutic resistance, as well as their interplay and potential mechanisms, providing promising insights and future directions in reversal of therapeutic resistance in cancer.

• Cancer
• Circular RNA
• Interplay
• N6-methyladenosine
• Therapeutic resistance

Platinum-based agents are one of the most widely used chemotherapy drugs for various types of cancer. However, one of the main challenges in the application of platinum drugs is resistance, which is currently being widely investigated. Epigenetic DNA methylation-based biomarkers are promising to aid in the selection of patients, helping to foresee their platinum therapy response in advance. These biomarkers enable minimally invasive patient sample collection, short analysis, and good sensitivity. Hence, improved methodologies for the detection and quantification of DNA methylation biomarkers will facilitate their use in the choice of an optimal treatment strategy.

Platinum-based chemotherapy is routinely used for the treatment of several cancers. Despite all the advances made in cancer research regarding this therapy and its mechanisms of action, tumor resistance remains a major concern, limiting its effectiveness. DNA methylation-based biomarkers may assist in the selection of patients that may benefit (or not) from this type of treatment and provide new targets to circumvent platinum chemoresistance, namely, through demethylating agents. We performed a systematic search of studies on biomarkers that might be predictive of platinum-based chemotherapy resistance, including in vitro and in vivo pre-clinical models and clinical studies using patient samples. DNA methylation biomarkers predictive of response to platinum remain mostly unexplored but seem promising in assisting clinicians in the generation of more personalized follow-up and treatment strategies. Improved methodologies for their detection and quantification, including non-invasively in liquid biopsies, are additional attractive features that can bring these biomarkers into clinical practice, fostering precision medicine.

• DNA methylation
• biomarker
• cancer
• epigenetics
• platinum-based chemotherapy

• Glioma
• chemosensitivity
• long non-coding RNAs
• microRNAs
• platinum drugs
• prognosis
• resistance mechanisms

• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Brain Neoplasms/drug therapy
• Brain Neoplasms/genetics
• Cisplatin/pharmacology
• Cisplatin/therapeutic use
• Drug Resistance, Neoplasm/genetics
• Glioma/drug therapy
• Glioma/genetics
• Humans
• MicroRNAs/genetics
• Platinum Compounds/pharmacology
• Platinum Compounds/therapeutic use
• RNA, Long Noncoding/genetics

• D. melanogaster
• NAD
• PARP
• RAS
• cancer biology
• caspase
• deacetylation
• glial cell
• neuroscience

• Animals
• Apoptosis
• Cell Proliferation
• Disease Models, Animal
• Drosophila Proteins/genetics
• Drosophila Proteins/metabolism
• Glioma/genetics
• Glioma/metabolism
• Nicotinamide-Nucleotide Adenylyltransferase/genetics
• Nicotinamide-Nucleotide Adenylyltransferase/metabolism
• Protein Processing, Post-Translational
• Tumor Suppressor Protein p53/metabolism

• National Natural Science Foundation of China
• Science and technology support program for youth innovation in universities of Shandong
• Sylvester Comprehensive Cancer Center
• Bohai Rim Advanced Research Institute for Drug Discovery (LX211011)

• DNA damage response
• anticancer drugs
• cisplatin
• cisplatin resistance

• Kozak sequence
• Micro-RNA
• Non-coding RNA
• Pre-mRNA methylation
• Pre-mRNA splicing
• RNA-binding proteins
• SR proteins
• Transcription factors
• mRNA processing

Cisplatin is a chemotherapeutic drug used for the treatment of a number of cancers. The efficacy of cisplatin relies on its binding to DNA and the induction of cytotoxic DNA damage to kill cancer cells. Cisplatin-based therapy is best known for curing testicular cancer; however, treatment of other solid tumors with cisplatin has not been as successful. Pre-clinical and clinical studies have revealed nucleotide excision repair (NER) as a major resistance mechanism against cisplatin in tumor cells. NER is a versatile DNA repair system targeting a wide range of helix-distorting DNA damage. The NER pathway consists of multiple steps, including damage recognition, pre-incision complex assembly, dual incision, and repair synthesis. NER proteins can recognize cisplatin-induced DNA damage and remove the damage from the genome, thereby neutralizing the cytotoxicity of cisplatin and causing drug resistance. Here, we review the molecular mechanism by which NER repairs cisplatin damage, focusing on the recent development of genome-wide cisplatin damage mapping methods. We also discuss how the expression and somatic mutations of key NER genes affect the response of cancer cells to cisplatin. Finally, small molecules targeting NER factors provide important tools to manipulate NER capacity in cancer cells. The status of research on these inhibitors and their implications in cancer treatment will be discussed.

• CSB
• DNA damage
• ERCC1-XPF
• XPA
• chemotherapy

Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3β), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.

Over the past decades, it is recognized that loss of DNA damage repair (DDR) pathways is an early and frequent event in tumorigenesis, occurring in 40-50% of many cancer types. The basis of synthetic lethality in cancer therapy is DDR deficient cancers dependent on backup DNA repair pathways. In cancer, the concept of synthetic lethality has been extended to pairs of genes, in which inactivation of one by deletion or mutation and pharmacological inhibition of the other leads to death of cancer cells whereas normal cells are spared the effect of the drug. The paradigm study is to induce cell death by inhibiting PARP in BRCA1/2 defective cells. Since the successful application of PARP inhibitor, a growing number of developed DDR inhibitors are ongoing in preclinical and clinical testing, including ATM, ATR, CHK1/2 and WEE1 inhibitors. Combination of PARP inhibitors and other DDR inhibitors, or combination of multiple components of the same pathway may have great potential synthetic lethality efficiency. As epigenetics joins Knudson’s two hit theory, silencing of DDR genes by aberrant epigenetic changes provide new opportunities for synthetic lethal therapy in cancer. Understanding the causative epigenetic changes of loss-of-function has led to the development of novel therapeutic agents in cancer. DDR and related genes were found frequently methylated in human cancers, including BRCA1/2, MGMT, WRN, MLH1, CHFR, P16 and APC. Both genetic and epigenetic alterations may serve as synthetic lethal therapeutic markers.

• BRCA1/2
• DNA damage repair
• Epigenetics
• PARP inhibitor
• Synthetic lethality

• Chemoresistance
• Platinum resistance
• Prognostic biomarker
• ovarian cancer

• Antineoplastic Agents/therapeutic use
• Biomarkers
• Drug Resistance, Neoplasm
• Female
• Humans
• Ovarian Neoplasms/drug therapy
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/mortality
• Platinum Compounds/therapeutic use
• Treatment Outcome

• DNA damage
• DNA repair
• chromatin remodeling
• epigenomics

• Chromatin Assembly and Disassembly/genetics
• Chromatin Assembly and Disassembly/physiology
• DNA Damage/genetics
• DNA Damage/physiology
• DNA Repair/genetics
• DNA Repair/physiology
• Epigenesis, Genetic/genetics
• Epigenesis, Genetic/physiology
• Humans

• Carcinogenesis
• DNA repair
• Helicobacter pylori
• Mismatch repair
• Nucleotide excision repair
• cagA

• Adult
• DNA Mismatch Repair
• DNA Repair
• DNA-Binding Proteins/genetics
• Endonucleases/genetics
• Female
• Gastritis/enzymology
• Gastritis/etiology
• Gastritis/genetics
• Gastritis/microbiology
• Gene Expression Regulation
• Gene Expression Regulation, Neoplastic
• Helicobacter Infections/complications
• Helicobacter pylori
• Humans
• Male
• Middle Aged
• Mismatch Repair Endonuclease PMS2/genetics
• Stomach Neoplasms/enzymology
• Stomach Neoplasms/etiology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology

• Apoptosis
• HT-29
• Pd(II) and Pt(II) complexes
• Thiazoline
• Tumor cells
• U-937

• Algorithms
• Bayes Theorem
• Beckwith-Wiedemann Syndrome/diagnosis
• Beckwith-Wiedemann Syndrome/genetics
• Beckwith-Wiedemann Syndrome/therapy
• Calibration
• Celiac Disease/diagnosis
• Celiac Disease/genetics
• Celiac Disease/therapy
• Computational Biology/methods
• CpG Islands/genetics
• DNA Methylation
• Genomic Imprinting
• Humans
• Potassium Channels, Voltage-Gated/genetics
• RNA, Long Noncoding/genetics
• Reproducibility of Results
• Sensitivity and Specificity
• Sequence Analysis, DNA/methods

• MC_UU_00002/7 Medical Research Council
• MR/S019669/1 Medical Research Council

• DNA repair
• LY2109761
• TGF-β
• glioma
• radiation

• Colitis
• Colon cancer
• Colorectal
• DNA damage response
• Inflammation
• Inflammatory bowel disease (IBD)

• 1p19q codeletion
• Chemosensitivity
• DNA repair genes
• Lower-grade gliomas

Caudal type homeobox 2 (CDX2) has been well-established as a diagnostic marker for colorectal cancer (CRC); however, less is known about its regulation, particularly its potential interactions with the DNA repair proteins, adenomatous polyposis coli (APC) and β-catenin, in a non-transcriptional manner. In the present study, the protein expression of CDX2 was analyzed, depending on the expression of the DNA repair proteins, mismatch repair (MMR), O6-methylguanine DNA methyltransferase (MGMT) and excision repair cross-complementing 1 (ERCC1), and its importance in Wnt signaling was also determined. A total of 101 liver metastases were punched into tissue microarray (TMA) blocks and serial sections were cut for immunohistochemistry. For each protein, an immunoreactive score was generated according to literature data and the scores were fitted to TMA. Subsequently, statistical analysis was performed to compare the levels of expression with each other and with clinical data. CDX2 loss of expression was observed in 38.5% of the CRC liver metastasis cases. A statistically significant association between CDX2 and each of the investigated MMRs was observed: MutL Homolog 1 (P<0.01), MutS protein Homolog (MSH) 2 (P<0.01), MSH6 (P<0.01), and postmeiotic segregation increased 2 (P=0.040). Furthermore, loss of MGMT and ERCC1 was also associated with CDX2 loss (P=0.039 and P<0.01, respectively). In addition, CDX2 and ERCC1 were inversely associated with metastatic tumor size (P=0.038 and P=0.027, respectively). Sustained CDX2 expression was associated with a higher expression of cytoplasmic/membranous β-catenin and with nuclear APC expression (P=0.042 and P<0.01, respectively). In conclusion, CDX2 loss of expression was not a rare event in liver metastasis of CRC and the results suggested that CDX2 may be involved in mechanisms resulting in the loss of DNA repair protein expression, and in turn methylation; however, its exact function in this context remains to be elucidated.

• DNA repair proteins
• caudal type homeobox 2
• colorectal cancer
• liver metastasis

The stability and integrity of the human genome are maintained by the DNA damage repair (DDR) system. Unrepaired DNA damage is a major source of potentially mutagenic lesions that drive carcinogenesis. In addition to gene mutation, DNA methylation occurs more frequently in DDR genes in human cancer. Thus, DNA methylation may play more important roles in DNA damage repair genes to drive carcinogenesis. Aberrant methylation patterns in DNA damage repair genes may serve as predictive, diagnostic, prognostic and chemosensitive markers of human cancer. MGMT methylation is a marker for poor prognosis in human glioma, while, MGMT methylation is a sensitive marker of glioma cells to alkylating agents. Aberrant epigenetic changes in DNA damage repair genes may serve as therapeutic targets. Treatment of MLH1-methylated colon cancer cell lines with the demethylating agent 5′-aza-2′-deoxycytidine induces the expression of MLH1 and sensitizes cancer cells to 5-fluorouracil. Synthetic lethality is a more exciting approach in patients with DDR defects. PARP inhibitors are the most effective anticancer reagents in BRCA-deficient cancer cells.

• DNA damage repair
• DNA methylation
• MGMT
• PARP inhibitor
• synthetic lethality

New hybrid nanoparticles permitted MRI monitoring of a cisplatin infusion while enhancing drug accumulation and DNA adduct formation in glioblastoma cells.

• Cancer therapy
• DNA repair
• Epigenetic silencing
• GADD45
• Genotoxic stress
• MGMT
• Promoter methylation
• TET
• p53
• tumor formation

• Animals
• CpG Islands/genetics
• DNA Methylation/genetics
• DNA Repair/genetics
• Epigenesis, Genetic/genetics
• Humans
• Neoplasms/genetics

Gliomas are primary tumors that originate in the brain or spinal cord and develop from supportive glial cells. The present study aimed to identify potential candidate molecular markers for the treatment of gliomas, and to explore the underlying mechanisms of this disease. The gene expression profile data GSE50021, which consisted of 10 specimens of normal brain tissues and 35 specimens of glioma tissues, was downloaded from Gene Expression Omnibus (GEO). The methylation microarray data GSE50022, consisting of 28 glioma specimens, was also downloaded from GEO. Differentially expressed genes (DEGs) between patients with glioma and normal individuals were identified, and key methylation sites were screened. Transcriptional regulatory networks were constructed, and target genes were selected. Survival analysis of key methylation sites and risk analysis of sub-pathways were performed, from which key genes and pathways were selected. A total of 79 DEGs and 179 key methylation sites were identified, of which 20 target genes and 36 transcription factors were included in the transcriptional regulatory network. Glutamate metabotropic receptor 2 (GRM2) was regulated by 8 transcription factors. Inositol-trisphosphate 3-kinase A (ITPKA) was a significantly enriched DEG, associated with the inositol phosphate metabolism pathway, Survival analysis revealed that the survival time of patients with lower methylation levels in cg00157228 was longer than patients with higher methylation levels. ITPKA was the closest located gene to cg00157228. In conclusion, GRM2 and enriched ITPKA, associated with the inositol phosphate metabolism pathway, may be key mechanisms in the development and progression of gliomas. Furthermore, the present study provided evidence for an additional mechanism of methylation-induced gliomas, in which methylation results in the dysregulation of specific transcripts. The results of the present study may provide a research direction for studying the mechanisms underlying the development and progression of gliomas.

• gliomas
• methylation
• sub-pathway

• DNA Repair Gene
• Glioma
• Meta-analysis
• Polymorphisms

• Animals
• Brain Neoplasms/diagnosis
• Brain Neoplasms/genetics
• DNA Repair/genetics
• Genetic Predisposition to Disease/genetics
• Glioma/diagnosis
• Glioma/genetics
• Humans
• Polymorphism, Single Nucleotide/genetics

• DNA methylation
• Pharmacoepigenetics
• epigenetics
• histone modifications
• interindividual drug response
• microRNA
• personalized medicine

Hyperplastic candidiasis is characterized by thickening of the mucosal epithelia with Candida albicans infection with occasional progression to squamous cell carcinoma (SCC). C. albicans is a critical factor in tumor development; however, the oncogenic mechanism is unclear. We have previously produced an animal model for hyperplastic candidiasis in the rat forestomach. In the present study, we investigate whether impaired DNA methylation and associated protein expression of tumor suppressor and DNA repair genes are involved in the SCC carcinogenesis process using this hyperplastic candidiasis model. Promoter methylation and protein expression were analyzed by methylation specific PCR and immunohistochemical staining, respectively, of 5 areas in the forestomachs of alloxan-induced diabetic rats with hyperplastic candidiasis: normal squamous epithelia, squamous hyperplasia, squamous hyperplasia adjacent to SCC, squamous hyperplasia transitioning to SCC, and SCC. We observed nuclear p16 overexpression despite increases in p16 gene promoter methylation during the carcinogenic process. TIMP3 and RAR-β2 promoter methylation progressed until the precancerous stage but disappeared upon malignant transformation. In comparison, TIMP3 protein expression was suppressed during carcinogenesis and RAR-β2 expression was attenuated in the cytoplasm but enhanced in nuclei. ERCC1 and BRCA1 promoters were not methylated at any stage; however, their protein expression disappeared beginning at hyperplasia and nuclear protein re-expression in SCC was observed only for ERCC1. These results suggest that aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 expression might occur that is inconsistent with the respective gene promoter methylation status, and that this overexpression might serve to promote the inflammatory carcinogenesis caused by C. albicans infection.

Although thousands of DNA damaging events occur in each cell every day, efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoiding the maintenance of mutations. The DNA repair enzymes continuously monitor the chromosomes to correct any damage that is caused by exogenous and endogenous mutagens. If DNA damage in proliferating cells is not repaired because of an inadequate expression of DNA repair genes, it might increase the risk of cancer. In addition to mutations, which can be either inherited or somatically acquired, epigenetic silencing of DNA repair genes has been associated with carcinogenesis. Gastric cancer represents the second highest cause of cancer mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes during the lifetime. Among the risk factors, Helicobacter pylori (H. pylori) infection is considered the main driving factor to gastric cancer development. Thus, in this review, we summarize the current knowledge of the role of H. pylori infection on the epigenetic regulation of DNA repair machinery in gastric carcinogenesis.

• Helicobacter pylori
• DNA repair
• Epigenetic
• DNA methylation
• Gastric cancer
• Histone modification

• Animals
• Cell Transformation, Neoplastic/genetics
• DNA Damage
• DNA Methylation
• DNA Repair
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Helicobacter Infections/complications
• Helicobacter Infections/microbiology
• Helicobacter pylori/genetics
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions
• Humans
• Risk Factors
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology
• Virulence/genetics

Deficiencies in DNA repair due to inherited germ-line mutations in DNA repair genes cause increased risk of gastrointestinal (GI) cancer. In sporadic GI cancers, mutations in DNA repair genes are relatively rare. However, epigenetic alterations that reduce expression of DNA repair genes are frequent in sporadic GI cancers. These epigenetic reductions are also found in field defects that give rise to cancers. Reduced DNA repair likely allows excessive DNA damages to accumulate in somatic cells. Then either inaccurate translesion synthesis past the un-repaired DNA damages or error-prone DNA repair can cause mutations. Erroneous DNA repair can also cause epigenetic alterations (i.e., epimutations, transmitted through multiple replication cycles). Some of these mutations and epimutations may cause progression to cancer. Thus, deficient or absent DNA repair is likely an important underlying cause of cancer. Whole genome sequencing of GI cancers show that between thousands to hundreds of thousands of mutations occur in these cancers. Epimutations that reduce DNA repair gene expression and occur early in progression to GI cancers are a likely source of this high genomic instability. Cancer cells deficient in DNA repair are more vulnerable than normal cells to inactivation by DNA damaging agents. Thus, some of the most clinically effective chemotherapeutic agents in cancer treatment are DNA damaging agents, and their effectiveness often depends on deficient DNA repair in cancer cells. Recently, at least 18 DNA repair proteins, each active in one of six DNA repair pathways, were found to be subject to epigenetic reduction of expression in GI cancers. Different DNA repair pathways repair different types of DNA damage. Evaluation of which DNA repair pathway(s) are deficient in particular types of GI cancer and/or particular patients may prove useful in guiding choice of therapeutic agents in cancer therapy.

• Epigenetic
• DNA damage
• DNA repair
• DNA repair deficiency disorders
• Epimutation
• Genomic instability
• Germ-line mutation
• MicroRNAs
• Precancerous conditions
• Gastrointestinal cancer

Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem as serial re-biopsy of primary tumours is often not a clinical option. MGMT (O⁶-methylguanine DNA methyltransferase) and APNG (alkylpurine-DNA-N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA damages and their levels in tissue are inversely related to treatment efficacy. Yet, serial clinical analysis remains difficult, and, when done, primarily relies on promoter methylation studies of tumour biopsy material at the time of initial surgery. Here we present a microfluidic chip to analyse mRNA levels of MGMT and APNG in enriched tumour exosomes obtained from blood. We show that exosomal mRNA levels of these enzymes correlate well with levels found in parental cells and that levels change considerably during treatment of seven patients. We propose that if validated on a larger cohort of patients, the method may be used to predict drug response in GBM patients.

Predicting and monitoring chemotherapy response remains a challenge for glioma treatment. Here the authors show that a microfluidic device can isolate glioma-derived exosomes from patient blood and accurately determine the levels of mRNA of key enzymes important for chemoresponsiveness.

The prognostic impact of excision repair cross-complementation group 1 (ERCC1) expression in gastric cancer (GC) has been investigated for decades, but has yielded controversial results. The aim of the present study was to provide a precise evaluation of whether the expression levels of ERCC1 are associated with overall survival (OS) in patients with GC. A systematic search of Medline and Embase was conducted. Original studies concerning OS and ERCC1 expression were included for critical appraisal. A total of 15 studies comprising 1,425 patients with GC were identified. The results revealed that high/positive ERCC1 expression was an indicator of poor survival in patients with GC [hazard ratio (HR) 1.48; 95% confidence interval (CI) 1.02–2.10; P=0.036; I²=83.8%; random-effects model] compared with low/negative ERCC1 expression. Subgroup analysis indicated that high/positive ERCC1 expression had a significant unfavorable impact on OS in the group of patients evaluated by reverse transcription polymerase chain reaction (RT-PCR; HR 2.57; 95% CI 1.49–4.45). Furthermore, high/positive ERCC1 expression was found to be associated with poor survival in patients receiving platinum-based chemotherapy in the RT-PCR group (HR 2.13; 95% CI 1.06–4.27). These data suggest that ERCC1 may be a useful prognostic factor for GC. In addition, low mRNA levels of ERCC1 appear to be associated with a significant favorable OS benefit from platinum-based chemotherapy.

• excision repair cross-complementation group 1
• gastric cancer
• meta-analysis

• ABCG2
• Acquired Cisplatin Resistance
• AhR
• Drug Transporters
• TCDD

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters/genetics
• ATP-Binding Cassette Transporters/metabolism
• Cell Line, Tumor
• Cell Survival/drug effects
• Cisplatin/pharmacology
• Drug Resistance, Neoplasm/drug effects
• Equilibrative-Nucleoside Transporter 2/genetics
• Equilibrative-Nucleoside Transporter 2/metabolism
• Humans
• Jurkat Cells
• K562 Cells
• Kaempferols/pharmacology
• Multidrug Resistance-Associated Proteins/genetics
• Multidrug Resistance-Associated Proteins/metabolism
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Polychlorinated Dibenzodioxins/pharmacology
• RNA, Messenger/metabolism
• Receptors, Aryl Hydrocarbon/metabolism
• Up-Regulation/drug effects
• Vault Ribonucleoprotein Particles/genetics
• Vault Ribonucleoprotein Particles/metabolism

DNA repair genes that have been inactivated by promoter methylation offer potential therapeutic targets either by targeting the specific repair deficiency, or by synthetic lethal approaches. This study evaluated promoter methylation status for eight selected DNA repair genes (ATM, BRCA1, ERCC1, MGMT, MLH1, NEIL1, RAD23B and XPC) in 56 non-small cell lung cancer (NSCLC) tumours and 11 lung cell lines using the methylation-sensitive high resolution melting (MS-HRM) methodology. Frequent methylation in NEIL1 (42%) and infrequent methylation in ERCC1 (2%) and RAD23B (2%) are reported for the first time in NSCLC. MGMT methylation was detected in 13% of the NSCLCs. Contrary to previous studies, methylation was not detected in ATM, BRCA1, MLH1 and XPC. Data from The Cancer Genome Atlas (TCGA) was consistent with these findings. The study emphasises the importance of using appropriate methodology for accurate assessment of promoter methylation.

• Animals
• Carcinogenesis/genetics
• Cell Cycle Checkpoints/genetics
• DNA Damage/genetics
• DNA Repair/genetics
• Humans
• Neoplasm Metastasis/genetics
• Neoplasm Metastasis/pathology
• Neoplasms/genetics
• Neoplasms/pathology

• P01 CA049062 NCI NIH HHS
• R01 CA130536 NCI NIH HHS
• R01CA130536 NCI NIH HHS
• R01GM079107 NIGMS NIH HHS
• R01 GM079107 NIGMS NIH HHS
• P01CA49062 NCI NIH HHS

• dihydropyrimidine dehydrogenase
• excision repair cross-complementing gene 1
• gastric cancer
• prognostic factor
• thymidylate synthase
• vascular endothelial growth factor

• ERCC3
• genetic polymorphism
• methylation
• microsomal epoxide hydrolase
• occupational exposure

• Benzene/toxicity
• China
• Cytochrome P-450 CYP1A1/genetics
• DNA Helicases/chemistry
• DNA Helicases/genetics
• DNA Methylation
• DNA-Binding Proteins/chemistry
• DNA-Binding Proteins/genetics
• Environmental Pollutants/toxicity
• Epoxide Hydrolases/genetics
• Female
• Genetic Predisposition to Disease
• Hematologic Diseases/chemically induced
• Hematologic Diseases/genetics
• Humans
• Male
• Middle Aged
• NAD(P)H Dehydrogenase (Quinone)/genetics
• Occupational Exposure
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic

Cisplatin is one of several chemotherapeutic drugs commonly used to treat esophageal cancer. Nucleotide excision repair (NER) pathway plays an important role in repairing cisplatin-caused DNA damage. It has been demonstrated recently that the key enzyme of this pathway, excision repair crosscomplimenting 1 (ERCC1), is a factor determining cisplatin resistance and patient's response to cisplatin treatment. Further studies on the relationship between ERCC1 and cisplatin resistance will improve our understanding of cisplatin resistance in patients with esophageal cancer.

• Excision repair cross-complimenting 1
• Cisplatin resistance
• Esophageal cancer