Telomere maintenance is one of the mechanisms ensuring indefinite divisions of cancer
and stem cells. Good understanding of telomere maintenance mechanisms (TMM) is
important for studying cancers and designing therapies. However, molecular factors
triggering selective activation of either the telomerase dependent (TEL) or the alternative
lengthening of telomeres (ALT) pathway are poorly understood. In addition, more
accurate and easy-to-use methodologies are required for TMM phenotyping. In this
study, we have performed literature based reconstruction of signaling pathways for the
ALT and TEL TMMs. Gene expression data were used for computational assessment
of TMM pathway activities and compared with experimental assays for TEL and
ALT. Explicit consideration of pathway topology makes bioinformatics analysis more
informative compared to computational methods based on simple summary measures
of gene expression. Application to healthy human tissues showed high ALT and TEL
pathway activities in testis, and identified genes and pathways that may trigger TMM
activation. Our approach offers a novel option for systematic investigation of TMM
activation patterns across cancers and healthy tissues for dissecting pathway-based
molecular markers with diagnostic impact.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84284 |
| Date | 24 March 2023 |
| Creators | Nersisyan, Lilit, Simonyan, Arman, Binder, Hans, Arakelyan, Arsen |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-8021, 662464 |
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