Promoter Methylation Status of DNA Repair Gene (hMLH1) in Gastric Carcinoma Patients of the Kashmir Valley

Wani, Majid; Afroze, Dil; Makhdoomi, Muzamil Ashraf; Hamid, Iqra; Wani, Bilal Ahmad; Bhat, G. A.; Wani, Rauf Ahmad; Wani, Khursheed Alam

doi:10.7314/apjcp.2012.13.8.4177

Cited by 25 publications

(11 citation statements)

References 28 publications

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“…P16 inhibits cell cycle progression, and has been found to correlate with poor tumor differentiation, lymph node metastasis and poor survival. The frequency and specificity of P16 were found to be 30.4–44.2 and 76–100%, respectively (15,18,20). RUNX3 belongs to the RUNX family of transcriptional factors, and has been found to correlate with depth of tumor invasion, lymph node and distant metastasis.…”

Section: Discussionmentioning

confidence: 95%

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Xie

Sun

et al. 2014

Oncology Letters

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Gastric cancer (GC) is one of the most frequently diagnosed malignancies in East Asia, particularly in China, and remains the second leading cause of cancer-associated mortality worldwide. However, no effective plasma biomarkers have been identified for the diagnosis of patients with GC. The aim of this study was to investigate the DNA methylation status of the ring finger protein 180 (RNF180), secreted frizzled-related protein 2 (SFRP2) and death-associated protein kinase 1 (DAPK1) genes in the plasma samples of 57 GC patients and 42 control individuals with no malignant disease, and to evaluate the clinical utility of these makers. A significantly higher level of methylation was observed in the plasma DNA of GC patients when compared with that of controls for the three genes investigated (RNF180, 57.89% vs. 23.81%; DAPK1, 49.12% vs. 28.57%; and SFRP2, 71.93% vs. 42.86%). No association was identified between the DAPK1 or SFRP2 methylation level in the plasma DNA and the clinicopathological parameters of patients. Notably, RNF180 methylation was found to positively correlate with tumor size (P=0.018), histological type (P=0.025), TNM stage (P=0.002), lymph node metastasis (P=0.008) and distant metastasis (P=0.018). Overall, 50 cancer patients (87.72%) exhibited methylation of at least one of the three markers, while 26 normal subjects presented methylation in plasma DNA [specificity, 38.1%; odds ratio (OR), 4.4]. The combined use of RNF180 and SFRP2 as methylation markers appeared to be the most preferable predictor with regard to predictive power and cost-performance (OR, 5.57; P=0.0002). The results of the present study indicate that aberrant promoter methylation of genes in the plasma may be detected in a substantial proportion of GC patients and thus, these genes must be evaluated in the screening and surveillance of GC.

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Section: Discussionmentioning

confidence: 95%

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Xie

Sun

et al. 2014

Oncology Letters

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“…15 In a study conducted with gastric carcinoma patients, researchers showed that mutL homolog 1 (MLH1) methylation was found to be more common in males (82.1%) compared to females (35.75%). 39 In the current study, male patients (81.25%) are composed of the majority of individuals in hypermethylation observed group. In addition, methylation of WT1, ESR1, CDH13, MSH6, CD44 and PAX5 genes were detected at a higher frequency in men compared to women.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of tumor suppressor genes in gastric cancer: associations with demographic and clinicopathological characteristics

et al. 2016

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“…These DNA repair genes (with DNA repair pathways indicated) were NEIL1 (BER), NEIL3 (BER), DCLRE1C (NHEJ), NHEJ1 (NHEJ), GTF2H5 (NER), and CCNH (NER). Lynam-Lennon et al [71] found that miR-31 is over- Colorectal [17] MGMT 46% 34% Colorectal [19] MGMT 47% 11% Colorectal [60] MGMT with MSI 70% 60% Colorectal [19] MSH2 13% 5% Colorectal [61] MBD4 Frequent Frequent Colorectal [62] ERCC1 100% 40% Colorectal [62] PMS2 88% 50% Colorectal [62] XPF 55% 40% Colorectal [63] WRN 29% 13% Stomach [64] MGMT 88% 78% Stomach [65] MLH1 73% 20% Esophagus [66] MLH1 77%-100% 23%-79% expressed in 47% of esophageal cancers and examined the consequences of over-expression of miR-31 in these cancers. Using a cell line, they first tested the effect of over-expression of miR-31 on the expression of 84 DNA repair genes.…”

Section: Dna Repair Genes In Gi Cancersmentioning

confidence: 97%

Epigenetic reduction of DNA repair in progression to gastrointestinal cancer

Bernstein

2015

WJGO

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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.

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Promoter Methylation Status of DNA Repair Gene (hMLH1) in Gastric Carcinoma Patients of the Kashmir Valley

Cited by 25 publications

References 28 publications

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Hypermethylation of tumor suppressor genes in gastric cancer: associations with demographic and clinicopathological characteristics

Epigenetic reduction of DNA repair in progression to gastrointestinal cancer

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