Epigenetic regulation in the carcinogenesis of cholangiocarcinoma

Chiang, Nai‐Jung; Shan, Yan Shen; Hung, Wen Chun; Chen, Li Tzong

doi:10.1016/j.biocel.2015.06.012

Cited by 19 publications

(11 citation statements)

References 49 publications

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“…Information related to the effect of altered histone modifications in CCA and to the response of CCA to epigenetic-based therapies is limited [81][82][83] .…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

“…On the other hand, several promoters of genes involved in Wnt signalling are hypermethylated in CCA tissue 90 . A number of publications strongly suggest that epi genetic changes are early events in the malignant process, linking the tumour epigenetics to the microenvironment 82 and opening up opportunities for early detection of CCA 83 .…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

See 1 more Smart Citation

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,073

1,139

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“…Information related to the effect of altered histone modifications in CCA and to the response of CCA to epigenetic-based therapies is limited [81][82][83] .…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Section: Epigenetic Modificationsmentioning

confidence: 99%

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,073

1,139

View full text Add to dashboard Cite

“…GA in this process have recently been implicated in the development of BTC (9). BAP1 encodes for a nuclear deubiquitinase, while PBRM1 and ARID1A both encode a subunit of the ATP dependent SWI/SNF chromatin-remodeling complexes (44,45). Jiao et al observed that mutations in at least one of these genes occurred in almost half of the BTCs sequenced in their study (9).…”

Section: Mutations In Chromatin Remodeling Genesmentioning

confidence: 99%

Molecular profiling of biliary tract cancer: a target rich disease

Jain¹,

Javle²

2016

J. Gastrointest. Oncol.

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Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 (), and genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients.

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“…A phase II randomized study investigating the use of the MEK inhibitor tramenitib vs. a fluoropyrimidine in patients with refractory BTC (SWOG 1310; ClinicalTrials.gov NCT02042443), has incorporated an expanded cytokine and immune cell analysis to confirm the above hypothesis. Finally, the MAPK pathway has been shown to influence epigenetic “drivers” of biliary tract carcinogenesis and future DNA methylation analysis may reveal patterns that would explain the selective clinical response to MEK inhibition in biliary cancer [ 21 - 23 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-exome tumor sequencing study in biliary cancer patients with a response to MEK inhibitors

et al. 2015

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We previously conducted a phase-II study with selumetinib (AZD6244), a small molecule inhibitor of MEK1/2, in advanced biliary tract cancers (BTC), where the primary endpoint was response rate. Several patients experienced objective response. These findings were confirmed with MEK162 in a similar patient population. To assess for tumor-specific genetic variants that mediate sensitivity to MEK inhibition in BTC, we performed whole-exome sequencing in patients with an objective response to selumetinib. Normal and tumor DNA from FFPE tissue from two patients who experienced an objective response underwent whole-exome sequencing. Raw sequence reads were processed with GATK workflow and tumor specific variants were identified using MuTect and VarScan2. Ensemble Variant Effect Predictor was used to determine functional consequences of these variants. Copy number changes and potential gene fusion events were also screened. Findings were compared to assess for any commonality between the two tumor samples, and whether the identified variants were intrinsic to the MAPK pathway. 1169 and 628 tumor-specific variants were identified in the two samples. Further analysis demonstrated 60 and 53 functional and novel variants, respectively. Of the identified tumor-specific variants, fusion events or copy number changes, no commonality was seen. Several variants in genes associated with ERK signaling were present in each tumor sample. Although there were no common tumor-specific variants in the two patients who exhibited an objective response to selumetinib, several genes associated with ERK signaling were identified. Confirmatory studies investigating the role of the identified genes and other potential tumor independent factors need further investigation.

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Epigenetic regulation in the carcinogenesis of cholangiocarcinoma

Cited by 19 publications

References 49 publications

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Molecular profiling of biliary tract cancer: a target rich disease

Whole-exome tumor sequencing study in biliary cancer patients with a response to MEK inhibitors

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