Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile

Kagohara, Luciane T.; Schussel, Juliana Lucena; Subbannayya, Tejaswini; Sahasrabuddhe, Nandini A.; LeBron, Cynthia; Brait, Mariana; Maldonado, Leonel; Valle, Blanca L.; Pirini, Francesca; Jahuira, Martha; López, Jaime; Letelier, Pablo; Brebi-Mieville, Priscilla; Ili, Carmen; Pandey, Akhilesh; Chatterjee, Aditi; Sidransky, David; Guerrero-Preston, Rafael

doi:10.2217/fon.14.165

Cited by 24 publications

(19 citation statements)

References 90 publications

(117 reference statements)

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“…Although hypermethylation of SSBP2 was observed in 9% (3 of 33 cases) of ovarian cancers, it was not statistically significant. Tsukamoto et al (18) found that methylation of the SSBP2 promoter was more frequently in gallbladder cancer than in cholecystitis. In addition, the oncogenic role of SSBP2 as a tumour promoter has also been suggested in glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

“…Although precise levels of LMO, LHX, and LIM-binding proteins are known to be critical for many developmental programs, accumulating evidence suggests that these complexes are also key molecules in various human cancers (13). The role of SSBP2 in human malignancies is an area of active investigation, and many studies have suggested that SSBP2 functions as a tumour suppressor and is silenced through a pathway mediated by promoter hypermethylation (14)(15)(16)(17)(18). However, among…”

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confidence: 99%

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Low Expression of Single-stranded DNA Binding Protein 2 (SSBP2) Predicts Unfavourable Postoperative Outcomes in Patients With Clear Cell Renal Cell Carcinoma

Kim

Bang

et al. 2019

In Vivo

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Background: Single-stranded DNA binding protein 2 (SSBP2) is a subunit of a single-stranded DNA binding complex, which is involved in the maintenance of hematopoietic stem cells and stress responses. Numerous studies have suggested that SSBP2 functions as a tumor suppressor and is silenced through a pathway mediated by promoter hypermethylation. However, the role of SSBP2 in human renal cell carcinoma has not been reported, to date. Herein, we investigated the clinicopathological significance of SSBP2 expression in clear cell renal cell carcinoma (ccRCC). Materials and Methods: We constructed tissue micro arrays consisting of 173 ccRCC tissues, and SSBP2 expression was evaluated semi-quantitatively based on the staining intensity and the proportion of stained cells. Regarding statistical analysis, the tissues were divided into two groups according to SSBP2 expression, and correlation of SSBP2 expression with various clinicopathological characteristics and patient outcomes was evaluated. Results: Low SSBP2 expression was observed in 114 of 175 (65.9%) of ccRCC cases, and low SSBP2 expression was significantly correlated with larger tumor size (p=0.005, Chi-square test), higher WHO/ISUP histological grade (p<0.001, Chi-square test), tumor necrosis (p=0.008, Chi-square test), sarcomatoid change (p=0.021, Chi-square test), and higher pT AJCC stage (p=0.002, Chi-square test). Kaplan-Meier survival curves revealed that patients with low SSBP2 expression had worse recurrence-free survival (p=0.041, log-rank test). Conclusion: ccRCC with low SSBP2 expression was associated with adverse clinicopathological characteristics and poor patient outcomes.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Low Expression of Single-stranded DNA Binding Protein 2 (SSBP2) Predicts Unfavourable Postoperative Outcomes in Patients With Clear Cell Renal Cell Carcinoma

Kim

Bang

et al. 2019

In Vivo

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“…CDKN2A/B genes are frequently mutated or amplified in iCCA (7–27%), 25 , 73 eCCAs (17–47%) 25 , 26 and GBC (19–26%), 25 , 74 while silencing via promoter methylation is also observed in BTCs. 74 , 75 In unresectable BTCs, the joint status of CDKN2A and p53 has been associated with a poor prognosis. 76 CCND1/3 mutations are observed across all BTCs (4–14%), as well CCNE1 mutations/amplifications (4–5% in eCCA/GBC) and RB1 mutations (1–7%).…”

Section: Rb-cell Cycle Dysregulationmentioning

confidence: 99%

Emerging role of precision medicine in biliary tract cancers

et al. 2018

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Biliary tracts cancers (BTCs) are a diverse group of aggressive malignancies with an overall poor prognosis. Genomic characterization has uncovered many putative clinically actionable aberrations that can also facilitate the prognostication of patients. As such, comprehensive genomic profiling is playing a growing role in the clinical management of BTCs. Currently however, there is only one precision medicine approved by the US Food and Drug Administration (FDA) for the treatment of BTCs. Herein, we highlight the prevalence and prognostic, diagnostic, and predictive significance of recurrent mutations and other genomic aberrations with current clinical implications or emerging relevance to clinical practice. Some ongoing clinical trials, as well as future areas of exploration for precision oncology in BTCs are highlighted.

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“…Genome-wide hypomethylation was the first described epigenetic aberration in cancer [ 26 ]. Loss of normal DNA methylation levels is associated with genome instability and aneuploidy, reactivation of transposable elements and loss of imprinting [ 26 , 27 ]. Nonetheless, hypermethylation is investigated more frequently.…”

Section: Reversible Epigenetic Eventsmentioning

confidence: 99%

Epigenetic regulation of gene expression in cancer: techniques, resources and analysis

Kagohara¹,

Stein-O’Brien²,

Kelley³

et al. 2017

Briefings in Functional Genomics

106

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Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways in even individual malignant cells. Epigenetic changes are critical mediators of these functional changes that drive and maintain the malignant phenotype. Changes in DNA methylation, histone acetylation and methylation, noncoding RNAs, posttranslational modifications are all epigenetic drivers in cancer, independent of changes in the DNA sequence. These epigenetic alterations were once thought to be crucial only for the malignant phenotype maintenance. Now, epigenetic alterations are also recognized as critical for disrupting essential pathways that protect the cells from uncontrolled growth, longer survival and establishment in distant sites from the original tissue. In this review, we focus on DNA methylation and chromatin structure in cancer. The precise functional role of these alterations is an area of active research using emerging high-throughput approaches and bioinformatics analysis tools. Therefore, this review also describes these high-throughput measurement technologies, public domain databases for high-throughput epigenetic data in tumors and model systems and bioinformatics algorithms for their analysis. Advances in bioinformatics data that combine these epigenetic data with genomics data are essential to infer the function of specific epigenetic alterations in cancer. These integrative algorithms are also a focus of this review. Future studies using these emerging technologies will elucidate how alterations in the cancer epigenome cooperate with genetic aberrations during tumor initiation and progression. This deeper understanding is essential to future studies with epigenetics biomarkers and precision medicine using emerging epigenetic therapies.

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Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile

Cited by 24 publications

References 90 publications

Low Expression of Single-stranded DNA Binding Protein 2 (SSBP2) Predicts Unfavourable Postoperative Outcomes in Patients With Clear Cell Renal Cell Carcinoma

Low Expression of Single-stranded DNA Binding Protein 2 (SSBP2) Predicts Unfavourable Postoperative Outcomes in Patients With Clear Cell Renal Cell Carcinoma

Emerging role of precision medicine in biliary tract cancers

Epigenetic regulation of gene expression in cancer: techniques, resources and analysis

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