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Article: The search for cis-regulatory driver mutations in cancer genomes

TitleThe search for cis-regulatory driver mutations in cancer genomes
Authors
KeywordsCis-regulation
Enhancer
Promoter
Somatic mutation
Cancer
Issue Date2015
Citation
Oncotarget, 2015, v. 6, n. 32, p. 32509-32525 How to Cite?
AbstractWith the advent of high-throughput and relatively inexpensive whole-genome sequencing technology, the focus of cancer research has begun to shift toward analyses of somatic mutations in non-coding cis-regulatory elements of the cancer genome. Cis-regulatory elements play an important role in gene regulation, with mutations in these elements potentially resulting in changes to the expression of linked genes. The recent discoveries of recurrent TERT promoter mutations in melanoma, and recurrent mutations that create a super-enhancer regulating TAL1 expression in T-cell acute lymphoblastic leukaemia (T-ALL), have sparked significant interest in the search for other somatic cis-regulatory mutations driving cancer development. In this review, we look more closely at the TERT promoter and TAL1 enhancer alterations and use these examples to ask whether other cis-regulatory mutations may play a role in cancer susceptibility. In doing so, we make observations from the data emerging from recent research in this field, and describe the experimental and analytical approaches which could be adopted in the hope of better uncovering the true functional significance of somatic cis-regulatory mutations in cancer.
Persistent Identifierhttp://hdl.handle.net/10722/250884
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPoulos, Rebecca C.-
dc.contributor.authorSloane, Mathew A.-
dc.contributor.authorHesson, Luke B.-
dc.contributor.authorWong, Jason W.H.-
dc.date.accessioned2018-02-01T01:53:59Z-
dc.date.available2018-02-01T01:53:59Z-
dc.date.issued2015-
dc.identifier.citationOncotarget, 2015, v. 6, n. 32, p. 32509-32525-
dc.identifier.urihttp://hdl.handle.net/10722/250884-
dc.description.abstractWith the advent of high-throughput and relatively inexpensive whole-genome sequencing technology, the focus of cancer research has begun to shift toward analyses of somatic mutations in non-coding cis-regulatory elements of the cancer genome. Cis-regulatory elements play an important role in gene regulation, with mutations in these elements potentially resulting in changes to the expression of linked genes. The recent discoveries of recurrent TERT promoter mutations in melanoma, and recurrent mutations that create a super-enhancer regulating TAL1 expression in T-cell acute lymphoblastic leukaemia (T-ALL), have sparked significant interest in the search for other somatic cis-regulatory mutations driving cancer development. In this review, we look more closely at the TERT promoter and TAL1 enhancer alterations and use these examples to ask whether other cis-regulatory mutations may play a role in cancer susceptibility. In doing so, we make observations from the data emerging from recent research in this field, and describe the experimental and analytical approaches which could be adopted in the hope of better uncovering the true functional significance of somatic cis-regulatory mutations in cancer.-
dc.languageeng-
dc.relation.ispartofOncotarget-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCis-regulation-
dc.subjectEnhancer-
dc.subjectPromoter-
dc.subjectSomatic mutation-
dc.subjectCancer-
dc.titleThe search for cis-regulatory driver mutations in cancer genomes-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.5085-
dc.identifier.pmid26356674-
dc.identifier.scopuseid_2-s2.0-84946046266-
dc.identifier.volume6-
dc.identifier.issue32-
dc.identifier.spage32509-
dc.identifier.epage32525-
dc.identifier.eissn1949-2553-
dc.identifier.isiWOS:000363186600033-
dc.identifier.issnl1949-2553-

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