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TCGA Pan-Cancer genomic analysis of Alternative Lengthening of Telomeres (ALT) related genes
- Source :
- Genes, Vol 11, Iss 834, p 834 (2020), Genes, Volume 11, Issue 7
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- Telomere maintenance mechanisms (TMM) are used by cancer cells to avoid apoptosis, 85&ndash<br />90% reactivate telomerase, while 10&ndash<br />15% use the alternative lengthening of telomeres (ALT). Due to anti-telomerase-based treatments, some tumors switch from a telomerase-dependent mechanism to ALT<br />in fact, the co-existence between both mechanisms has been observed in some cancers. Although different elements in the ALT pathway are uncovered, some molecular mechanisms are still poorly understood. Therefore, with the aim to identify potential molecular markers for the study of ALT, we combined in silico approaches in a 411 telomere maintenance gene set. As a consequence, we conducted a genomic analysis of these genes in 31 Pan-Cancer Atlas studies from The Cancer Genome Atlas and found 325,936 genomic alterations<br />from which, we identified 20 genes highly mutated in the cancer studies. Finally, we made a protein-protein interaction network and enrichment analysis to observe the main pathways of these genes and discuss their role in ALT-related processes, like homologous recombination and homology directed repair. Overall, due to the lack of understanding of the molecular mechanisms of ALT cancers, we proposed a group of genes, which after ex vivo validations, could represent new potential therapeutic markers in the study of ALT.
- Subjects :
- 0301 basic medicine
Telomerase
lcsh:QH426-470
ALT
In silico
Telomere-Binding Proteins
Genomics
Computational biology
Biology
Article
Homology directed repair
03 medical and health sciences
0302 clinical medicine
Telomere Maintenance Gene
Neoplasms
Genetics
Humans
cancer
Genetic Predisposition to Disease
Protein Interaction Maps
Gene
Genetics (clinical)
Telomere Homeostasis
telomeres
Telomere
lcsh:Genetics
030104 developmental biology
in silico
030220 oncology & carcinogenesis
Cancer cell
Homologous recombination
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Genes, Vol 11, Iss 834, p 834 (2020), Genes, Volume 11, Issue 7
- Accession number :
- edsair.doi.dedup.....5fe29a7948692ff4deeb4ed18f84e478
- Full Text :
- https://doi.org/10.1101/2020.04.27.063610