DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study

Lin, Hsing Ying; Hung, Shih‐Kai; Lee, Moon Sing; Chiou, Wen‐Yen; Huang, Tze Ta; Tseng, Chih En; Shih, Liang Yu; Lin, Ru Inn; Lin, Jora M. J.; Lai, Yi Hui; Chang, Chia Bin; Hsu, Feng Chun; Chen, Liang Cheng; Tsai, Shiang Jiun; Su, Yu Chieh; Lai, Hung Chih; Hsu, Wen Lin; Liu, Dai Wei; Tai, Chien‐Kuo; Wu, Shu Fen; Chan, Michael W.Y.

doi:10.18632/oncotarget.2821

Cited by 25 publications

(34 citation statements)

References 72 publications

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“…Further support for the role of FHIT in the DDR comes from DNA methylome analysis showing that epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer [77]. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models and resensitized radioresistant cancer cells to irradiation by restoring Chk2 phosphorylation and G2/M arrest [77].…”

Section: Cfs Gene Products With Roles In the Ddrmentioning

confidence: 99%

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Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response

2016

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The role of common fragile sites (CFSs) in cancer remains controversial. Two main views dominate the discussion: one suggests that CFS loci are hotspots of genomic instability leading to inactivation of genes encoded within them, while the other view proposes that CFSs are functional units and that loss of the encoded genes confers selective pressure, leading to cancer development. The latter view is supported by emerging evidence showing that expression of a given CFS is associated with genome integrity and that inactivation of CFS-resident tumor suppressor genes leads to dysregulation of the DNA damage response (DDR) and increased genomic instability. These two viewpoints of CFS function are not mutually exclusive but rather coexist; when breaks at CFSs are not repaired accurately, this can lead to deletions by which cells acquire growth advantage because of loss of tumor suppressor activities. Here, we review recent advances linking some CFS gene products with the DDR, genomic instability, and carcinogenesis and discuss how their inactivation might represent a selective advantage for cancer cells.

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Section: Cfs Gene Products With Roles In the Ddrmentioning

confidence: 99%

“…Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models and resensitized radioresistant cancer cells to irradiation by restoring Chk2 phosphorylation and G2/M arrest [77]. …”

Section: Cfs Gene Products With Roles In the Ddrmentioning

confidence: 99%

Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response

2016

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“…Recently, a study found that high expression of MUC13 was associated with deceased expression of tumor suppressor, p53, and also the activation or expression of crucial oncogenes, HER2, PAK1, ERK, Akt, and S100A4 [16]. Another study demonstrated that miR-145 can suppress tumor growth of pancreatic cancer through its inhibitory effects on MUC13 [31]. These implied that MUC13 might become an effective therapeutic target for cancer.…”

Section: Discussionmentioning

confidence: 99%

High expression of Mucin13 associates with grimmer postoperative prognosis of patients with non-metastatic clear-cell renal cell carcinoma

Liu

Yang

et al. 2016

Oncotarget

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BackgroundMucin13 (MUC13) is a transmembrane glycoprotein that is aberrantly expressed in ovarian and gastro-intestinal tumors, but its role in renal cell carcinoma remains elusive. The purpose of this study is to evaluate the prognostic value of MUC13 expression in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) after surgical resection.ResultsMUC13 high expression was associated with high Fuhrman grade (p < 0.001), high SSIGN score (p = 0.011), early recurrence (p < 0.001) and poor survival (p < 0.001). Multivariate Cox regression analysis identified MUC13 expression as an independent prognostic factor for RFS and OS of ccRCC patients. A nomogram integrating MUC13 expression and other independent prognosticators was established to predict RFS and OS of ccRCC patients. Optimal agreement was shown between the predictions and observations in calibration curves.Matrials and methodsThis study enrolled 410 postoperative non-metastatic ccRCC patients at a single institution. Clinicopathologic variables, recurrence-free survival (RFS), and overall survival (OS) were recorded. MUC13 expression was detected by immunohistochemical staining in tumor specimens. Association of MUC13 expression with clinicopathological factors was explored. Kaplan-Meier analysis was performed to compare survival curves. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on RFS and OS. A prognostic nomogram was constructed based on the independent prognostic factors identified by multivariate analysis.ConclusionsMUC13 high expression is a novel independent adverse prognostic factor of clinical outcome in non-metastatic ccRCC patients after surgery.

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“…Fragile histidine triad ( FHIT ) gene regulates G2/M checkpoint and is located in a fragile chromosome site (3p13.2), which would likely be damaged by ionizing irradiation, Lin et al6 selected it for study. In oral carcinoma cell lines, the promoter of FHIT gene was hyper‐methylated in radio‐resistant cells.…”

Section: Radio‐sensitivity and Dna Methylation Of Cell Cycle‐related mentioning

confidence: 99%

“…However, parts of patients with above tumors are resistant to irradiation or some initially sensitive patients develop into irradiation resistance. Hence, irradiation resistance is 1 of the major obstacles that leads to loco‐regional recurrence of malignant tumors during treatment 2, 3, 4, 5, 6…”

Section: Introductionmentioning

confidence: 99%

The pivotal role of DNA methylation in the radio‐sensitivity of tumor radiotherapy

et al. 2018

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Radiotherapy is an important modality for treatment of carcinomas; however, radio‐resistance is still a difficult problem. Aberrant epigenetic alterations play an important role in cancer development. Among epigenetic parameters, DNA methylation has arguably attracted the most attention in the radio‐resistance process. To determine the role of DNA methylation in radiation resistance, several studies were conducted. We summarized previous studies on the role of DNA methylation in radiotherapy. We observed this significant role of DNA methylation in genes related to DNA repair, cell proliferation, cell cycle process, and re‐oxygenation. Furtherly, we also conclude the predictive effect of DNA methylation on tumor radio‐sensitivity and the using of DNA methyltransferase inhibitors in clinical practice. DNA methylation plays a pivotal role in the radio‐sensitivity of tumor radio‐therapy. While hyper‐methylation or hypo‐methylation of genes is related to gene functions.

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DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study

Cited by 25 publications

References 72 publications

Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response

Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response

High expression of Mucin13 associates with grimmer postoperative prognosis of patients with non-metastatic clear-cell renal cell carcinoma

The pivotal role of DNA methylation in the radio‐sensitivity of tumor radiotherapy

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