Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history

Kim, J.J.; Chung, Siu-Wah; Kim, J.W.; Oh, Jong Sik; Kim, S.; Song, Sang Yong; Park, J.; Kim, D.-H.

doi:10.1093/annonc/mdl018

Cited by 30 publications

(24 citation statements)

References 31 publications

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“…Genomic DNA was extracted from fresh-frozen tissues of hepatocellular carcinoma as previously described (17). Methylationspecific PCR was done to analyze the methylation status of seven genes, as previously described by Herman et al (Fig.…”

Section: Methodsmentioning

confidence: 99%

Promoter Hypermethylation of the p16 Gene Is Associated with Poor Prognosis in Recurrent Early-Stage Hepatocellular Carcinoma

Kim

Kim³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Despite significant advances in the detection and treatment of hepatocellular carcinoma, the prognosis of patients with hepatocellular carcinoma remains very poor, in part due to the high incidence of recurrence. This study was aimed at identifying a prognostic indicator of recurrence in patients with hepatocellular carcinoma. We retrospectively analyzed CpG island hypermethylation of the p14, p15, p16, GSTP1, integrin a4, SYK, and CDH1 genes in fresh-frozen tissues from 265 patients with hepatocellular carcinoma using the methylation-specific PCR. The expression levels of p16 and p53 were evaluated by immunohistochemistry. CpG island hypermethylation was detected in 6% for p14, 21% for p15, 67% for p16, 75% for GSTP1, 23% for integrin a4 , 12% for SYK , and 57% for CDH1 . Recurrence was observed in 102 (38%) of the 265 patients. There was no association between the risk for recurrence and hypermethylation of any gene studied. However, p16 methylation was associated with a poor survival after surgery for recurrent stage I to II hepatocellular carcinomas (hazard ratio, 4.05; 95% confidence interval, 1.15-14.20; P = 0.03). In addition, the hazard of failure after recurrence was about 3.80 (95% confidence interval, 1.03-14.20; P = 0.04) times higher in patients with p16 methylation than in those without. Negative expression of p16 at a protein level was also associated with poor survival in recurrent stage I to II hepatocellular carcinomas, but p53 expression did not have a synergistic effect on the poor prognosis. In conclusion, the present study suggests that p16 methylation may be associated with a poor prognosis in recurrent early-stage hepatocellular carcinomas. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2260 -7)

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Section: Methodsmentioning

confidence: 99%

Promoter Hypermethylation of the p16 Gene Is Associated with Poor Prognosis in Recurrent Early-Stage Hepatocellular Carcinoma

Kim

Kim³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…High methylation of tumor-related genes was associated with later stages of gastric cancer, but HLTF methylation status was not associated with the tumor stage in most series [59,[70][71][72][73][74][75][76]. HLTF promoter hypermethylation appears at an early stage in gastric carcinogenesis in patients with a family history of gastric cancers and might constitute a risk marker for gastric cancer in these families.…”

Section: Hltf Silencing Through Promoter Hypermethylationmentioning

confidence: 99%

The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?

Dhont

Mascaux

Belayew

2015

Cell. Mol. Life Sci.

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The Helicase-like Transcription Factor (HLTF) belongs to the SWI/SNF family of proteins involved in chromatin remodeling. In addition to its role in gene transcription, HLTF has been implicated in DNA repair, which suggests that this protein acts as a tumor suppressor. Accumulating evidence indicates that HLTF expression is altered in various cancers via two mechanisms: gene silencing through promoter hypermethylation or alternative mRNA splicing, which leads to the expression of truncated proteins that lack DNA repair domains. In either case, the alteration of HLTF expression in cancer has a poor prognosis. In this review, we gathered published clinical and molecular data on HLTF. Our purposes are (a) to address whether HLTF alterations could be considered as cancer drivers or passengers and (b) to determine whether its different functions (transcription or DNA repair) could be diverted in clonal selection during cancer progression.

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“…By ensuring the completion of S-phase following DNA damage, Rad5/HLTF/SHPRH contribute to genome integrity. HLTF is a DNA-binding protein (39-41) first described as a transcription factor (42,43), but later authenticated as a protein involved in DNA repair, in tumor suppression, and in the early stages of carcinogenesis (44)(45)(46)(47). Although both HLTF and SHPRH are able to polyubiquitinate PCNA, they do not act redundantly (48).…”

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confidence: 99%

HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages

Lahouassa

Blondot

Chauveau

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Viruses often interfere with the DNA damage response to better replicate in their hosts. The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) protein has been reported to modulate the activity of the DNA repair structure-specific endonuclease subunit (SLX4) complex and to promote cell cycle arrest. Vpr also interferes with the base-excision repair pathway by antagonizing the uracil DNA glycosylase (Ung2) enzyme. Using an unbiased quantitative proteomic screen, we report that Vpr down-regulates helicase-like transcription factor (HLTF), a DNA translocase involved in the repair of damaged replication forks. Vpr subverts the DDB1-cullin4-associatedfactor 1 (DCAF1) adaptor of the Cul4A ubiquitin ligase to trigger proteasomal degradation of HLTF. This event takes place rapidly after Vpr delivery to cells, before and independently of Vpr-mediated G2 arrest. HLTF is degraded in lymphocytic cells and macrophages infected with Vpr-expressing HIV-1. Our results reveal a previously unidentified strategy for HIV-1 to antagonize DNA repair in host cells.HIV | restriction factor | DNA repair | Vpr target | SILAC

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Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history

Abstract: These results suggest that HLTF methylation may play a crucial role in the early stages of gastric carcinogenesis in patients with family histories and may be a valuable susceptible marker for the risk of gastric cancer in individuals with family histories.

Cited by 30 publications

References 31 publications

Promoter Hypermethylation of the p16 Gene Is Associated with Poor Prognosis in Recurrent Early-Stage Hepatocellular Carcinoma

Promoter Hypermethylation of the p16 Gene Is Associated with Poor Prognosis in Recurrent Early-Stage Hepatocellular Carcinoma

The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?

HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages

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