Show simple item record

dc.contributor.authorLee, M
dc.contributor.authorTeber, ET
dc.contributor.authorHolmes, O
dc.contributor.authorNones, K
dc.contributor.authorPatch, A-M
dc.contributor.authorDagg, RA
dc.contributor.authorLau, LMS
dc.contributor.authorLee, JH
dc.contributor.authorNapier, CE
dc.contributor.authorArthur, JW
dc.contributor.authorGrimmond, SM
dc.contributor.authorHayward, NK
dc.contributor.authorJohansson, PA
dc.contributor.authorMann, GJ
dc.contributor.authorScolyer, RA
dc.contributor.authorWilmott, JS
dc.contributor.authorReddel, RR
dc.contributor.authorPearson, JV
dc.contributor.authorWaddell, N
dc.contributor.authorPickett, HA
dc.date.accessioned2020-12-17T03:46:35Z
dc.date.available2020-12-17T03:46:35Z
dc.date.issued2018-06-01
dc.identifierpii: 4990019
dc.identifier.citationLee, M., Teber, E. T., Holmes, O., Nones, K., Patch, A. -M., Dagg, R. A., Lau, L. M. S., Lee, J. H., Napier, C. E., Arthur, J. W., Grimmond, S. M., Hayward, N. K., Johansson, P. A., Mann, G. J., Scolyer, R. A., Wilmott, J. S., Reddel, R. R., Pearson, J. V., Waddell, N. & Pickett, H. A. (2018). Telomere sequence content can be used to determine ALT activity in tumours. NUCLEIC ACIDS RESEARCH, 46 (10), pp.4903-4918. https://doi.org/10.1093/nar/gky297.
dc.identifier.issn0305-1048
dc.identifier.urihttp://hdl.handle.net/11343/255025
dc.description.abstractThe replicative immortality of human cancer cells is achieved by activation of a telomere maintenance mechanism (TMM). To achieve this, cancer cells utilise either the enzyme telomerase, or the Alternative Lengthening of Telomeres (ALT) pathway. These distinct molecular pathways are incompletely understood with respect to activation and propagation, as well as their associations with clinical outcomes. We have identified significant differences in the telomere repeat composition of tumours that use ALT compared to tumours that do not. We then employed a machine learning approach to stratify tumours according to telomere repeat content with an accuracy of 91.6%. Importantly, this classification approach is applicable across all tumour types. Analysis of pathway mutations that were under-represented in ALT tumours, across 1,075 tumour samples, revealed that the autophagy, cell cycle control of chromosomal replication, and transcriptional regulatory network in embryonic stem cells pathways are involved in the survival of ALT tumours. Overall, our approach demonstrates that telomere sequence content can be used to stratify ALT activity in cancers, and begin to define the molecular pathways involved in ALT activation.
dc.languageEnglish
dc.publisherOXFORD UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.titleTelomere sequence content can be used to determine ALT activity in tumours
dc.typeJournal Article
dc.identifier.doi10.1093/nar/gky297
melbourne.affiliation.departmentCentre for Cancer Research
melbourne.source.titleNucleic Acids Research
melbourne.source.volume46
melbourne.source.issue10
melbourne.source.pages4903-4918
dc.rights.licenseCC BY-NC
melbourne.elementsid1328821
melbourne.contributor.authorGrimmond, Sean
dc.identifier.eissn1362-4962
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record