Frequent Downregulation and Promoter Hypermethylation of DLC1: Relationship with Clinical Outcome in Gallbladder Cancer

Abstract MLL-rearranged infant acute lymphoblastic leukemia (ALL) remains the most aggressive type of childhood leukemia, displaying a unique gene expression profile. Here we hypothesized that this characteristic gene expression signature may have been established by potentially reversible epigenetic modifications. To test this hypothesis, we used differential methylation hybridization to explore the DNA methylation patterns underlying MLL-rearranged ALL in infants. The obtained results were correlated with gene expression data to confirm gene silencing as a result of promoter hypermethylation. Distinct promoter CpG island methylation patterns separated different genetic subtypes of MLL-rearranged ALL in infants. MLL translocations t(4;11) and t(11;19) characterized extensively hypermethylated leukemias, whereas t(9;11)-positive infant ALL and infant ALL carrying wild-type MLL genes epigenetically resembled normal bone marrow. Furthermore, the degree of promoter hypermethylation among infant ALL patients carrying t(4;11) or t(11;19) appeared to influence relapse-free survival, with patients displaying accentuated methylation being at high relapse risk. Finally, we show that the demethylating agent zebularine reverses aberrant DNA methylation and effectively induces apoptosis in MLL-rearranged ALL cells. Collectively these data suggest that aberrant DNA methylation occurs in the majority of MLL-rearranged infant ALL cases and guides clinical outcome. Therefore, inhibition of aberrant DNA methylation may be an important novel therapeutic strategy for MLL-rearranged ALL in infants.

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p16INK4Aand p14ARFGene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review

Disease Markers ◽

10.1155/2014/260549 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 27

Author(s):

A. Al-Kaabi ◽

L. W. van Bockel ◽

A. J. Pothen ◽

S. M. Willems

Keyword(s):

Squamous Cell Carcinoma ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Squamous Cell ◽

Methylation Status ◽

Gene Promoter ◽

Promoter Hypermethylation ◽

Oropharyngeal Squamous Cell Carcinoma ◽

Molecular Profile ◽

Tumor Type

Head and neck squamous cell carcinoma is a heterogeneous group of tumors with each subtype having a distinct histopathological and molecular profile. Most tumors share, to some extent, the same multistep carcinogenic pathways, which include a wide variety of genetic and epigenetic changes. Epigenetic alterations represent all changes in gene expression patterns that do not alter the actual DNA sequence. Recently, it has become clear that silencing of cancer related genes is not exclusively a result of genetic changes such as mutations or deletions, but it can also be regulated on epigenetic level, mostly by means of gene promoter hypermethylation. Results from recent studies have demonstrated that DNA methylation patterns contain tumor-type-specific signatures, which could serve as biomarkers for clinical outcome in the near future. The topic of this review discusses gene promoter hypermethylation in oral and oropharyngeal squamous cell carcinoma (OSCC). The main objective is to analyse the available data on gene promoter hypermethylation of the cell cycle regulatory proteinsp16INK4Aandp14ARFand to investigate their clinical significance as novel biomarkers in OSCC. Hypermethylation of both genes seems to possess predictive properties for several clinicopathological outcomes. We conclude that the methylation status ofp16INK4Ais definitely a promising candidate biomarker for predicting clinical outcome of OSCC, especially for recurrence-free survival.

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Frequent Promoter Hypermethylation and Down Regulation of BNIP3: An Early Event During Gallbladder Cancer Progression

10.21203/rs.3.rs-270934/v1 ◽

2021 ◽

Author(s):

Amisha Bharti ◽

Deepika Singh ◽

Mumtaz A Ansari ◽

Mallika Tewari ◽

Gopeshwar Narayan ◽

...

Keyword(s):

Gallbladder Cancer ◽

Cancer Progression ◽

Methylation Status ◽

Promoter Hypermethylation ◽

Nodal Metastasis ◽

Early Event ◽

Down Regulation ◽

Interacting Protein ◽

Apoptotic Protein ◽

Adenovirus E1b

Abstract Epigenetic alterations have been reported as one of the risk factors of Gallbladder cancer (GBC). Promoter hypermethylation is associated with high incidence and poor prognosis of GBC. Bcl‑2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is a pro-apoptotic protein member of Bcl‑2 family. Present study was aimed to investigate expression profile and promoter methylation status of BNIP3 in GBC and its correlation with clinico-pathological parameters. We demonstrate down regulation of BNIP3 in 56% of the GBC samples. BNIP3 promoter is also frequently hypermethylated (69%) in GBC samples. Interestingly, we found that 69% (40/58) of the BNIP3 promoter hypermethylated samples had also reduced expression of BNIP3. Our data demonstrate significant correlation of the mRNA expression and promoter hypermethylation with late stage and nodal metastasis. Hypermethylation of BNIP3 promoter is associated with low overall survival period. Our results suggest that promoter hypermethylation is an early event and can be a frequent mechanism for down regulation of BNIP3 in GBC. BNIP3 can be a good prognostic and diagnostic marker of GBC.

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DNA methylation of SFRP1, SFRP2, and WIF1 and prognosis of postoperative colorectal cancer patients

BMC Cancer ◽

10.1186/s12885-019-6436-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Xinyan Liu ◽

Jinming Fu ◽

Haoran Bi ◽

Anqi Ge ◽

Tingting Xia ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Methylation ◽

Clinical Outcome ◽

Promoter Methylation ◽

Cox Regression ◽

Wnt Signaling Pathway ◽

Promoter Hypermethylation ◽

Tumor Tissues ◽

Potential Possibility ◽

Favorable Clinical Outcome

Abstract Background As biomarkers, DNA methylation is used to detect colorectal cancer (CRC) and make assessment of CRC prognosis. The published findings showed the association between the methylation of SFRP1, SFRP2, and WIF1, located in the Wnt signaling pathway, and the prognosis of CRC were not consistent. Our study aimed to explore the potential possibility of SFRP1, SFRP2, and WIF1 concomitant promoter methylation as prognostic biomarkers of postoperative CRC patients. Methods As a total of 307 sporadic postoperative CRC patients were followed up, we detected SFRP1, SFRP2, and WIF1 methylation obtained from tumor tissues and adjacent non-tumor tissues respectively on the basis of methylation-sensitive high resolution melting analysis. Univariate and multivariate Cox regressions were carried out so as to assess the potential possibility of SFRP1, SFRP2, and WIF1 promoter methylation as predictors of prognosis. Confounders in our study were controlled by Propensity Score (PS) analysis. Results The SFRP1, SFRP2, and WIF1 methylation levels in tumor tissues were significantly higher than that in adjacent non-tumor tissues (P < 0.001). SFRP2 hypermethylation was significantly associated with a favorable clinical outcome at the hazard ratio (HR) of 0.343 [95% confidence intervals (CI): 0.164–0.718, P = 0.005] and 0.410 (95% CI: 0.200–0.842, P = 0.015) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1 and SFRP2 was significantly associated with a favorable clinical outcome at the HR of 0.333 (95% CI: 0.159–0.694, P = 0.003) and 0.398 (95% CI: 0.192–0.821, P = 0.013) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1, SFRP2 and WIF1 was significantly associated with a favorable clinical outcome at the HR of 0.326 (95% CI: 0.117–0.908, P = 0.032) and 0.401 (95% CI: 0.146–1.106, P = 0.077) in multivariate Cox regression and PS analysis, respectively. Conclusions SFRP1, SFRP2, and WIF1 were frequently hypermethylated in CRC tumor tissues. It was apparent that the promoter hypermethylation of SFRP2 and co-hypermethylation of SFRP1 and SFRP2 might be considered as independent prognostic predictors for survival advantage of postoperative CRC patients.

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Spontaneous Hepatic Infarction in a Patient with Gallbladder Cancer

Case Reports in Oncology ◽

10.1159/000446911 ◽

2016 ◽

Vol 9 (2) ◽

pp. 321-327 ◽

Cited By ~ 1

Author(s):

Kang Min Lee ◽

Hannah Joung ◽

Jung Won Heo ◽

Seo Kyung Woo ◽

In Sook Woo ◽

...

Keyword(s):

Clinical Outcome ◽

Gallbladder Cancer ◽

Biliary Cancer ◽

Disease Entity ◽

Invasive Procedures ◽

Fatal Complication ◽

Patients With Cancer ◽

Anticoagulation Treatment ◽

Hepatic Infarction ◽

Biliary Malignancies

Hepatic infarction is known as a rare disease entity in nontransplant patients. Although a few cases of hepatic infarction have been reported to be linked with invasive procedures, trauma, and hypercoagulability, a case of spontaneous hepatic infarction in a nontransplanted patient has hardly ever been reported. However, many clinical situations of patients with cancer, in particular biliary cancer, can predispose nontransplant patients to hepatic infarction. Besides, the clinical outcome of hepatic infarction in patients with cancer can be worse than in patients with other etiologies. As for treatment, anticoagulation treatment is usually recommended. However, because of its multifactorial etiology and combined complications, treatment of hepatic infarction is difficult and not simple. Herein, we report a case of fatal hepatic infarction that occurred spontaneously during the course of treatment in a patient with gallbladder cancer. Hepatic infarction should be considered as a possible fatal complication in patients during treatment of biliary malignancies.

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