Alternative Lengthening of Telomeres (ALT)

Stable Identifier
Homo sapiens
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Alternative lengthening of telomeres (ALT) is a homologous recombination repair-directed telomere synthesis that takes place in 5-15% of tumors. ALT positive tumors often harbor loss-of-function mutations in ATRX (Alpha thalassemia mental retardation X-linked) or, more rarely, DAXX (Death domain-associated protein 6) chromatin remodeling factors, which may act to inhibit DNA recombination at telomere ends (reviewed by Gocha et al. 2013). The nuclear receptor complex NuRD-ZNF827 contributes to the recruitment of homologous recombination (HR) machinery to telomeres (Conomos et al. 2014). ALT is most prevalent in subsets of sarcomas, including osteosarcomas and some soft tissue sarcomas, brain cancers and neuroblastomas (Heaphy et al. 2011, Arora and Azzalin 2015). For review, please refer to Nabetani and Ishikawa 2011, Pickett and Reddel 2015, Verma and Greenberg 2016, Amorim et al. 2016, Sommer and Royle 2020, Zhang and Zou 2020.
Literature References
PubMed ID Title Journal Year
27657132 The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype

Santos, G, Soares, P, Vinagre, J, Amorim, JP

Genes (Basel) 2016
32175073 Alternative lengthening of telomeres: from molecular mechanisms to therapeutic outlooks

Zhang, JM, Zou, L

Cell Biosci 2020
25150861 NuRD-ZNF827 recruitment to telomeres creates a molecular scaffold for homologous recombination

Reddel, RR, Conomos, D, Pickett, HA

Nat. Struct. Mol. Biol. 2014
20937668 Alternative lengthening of telomeres pathway: recombination-mediated telomere maintenance mechanism in human cells

Ishikawa, F, Nabetani, A

J. Biochem. 2011
27222516 Noncanonical views of homology-directed DNA repair

Verma, P, Greenberg, RA

Genes Dev. 2016
32012790 ALT: A Multi-Faceted Phenomenon

Sommer, A, Royle, NJ

Genes (Basel) 2020
23219603 Alternative mechanisms of telomere lengthening: permissive mutations, DNA repair proteins and tumorigenic progression

Groden, J, Gocha, AR, Harris, J

Mutat. Res. 2013
26158306 Telomere elongation chooses TERRA ALTernatives

Arora, R, Azzalin, CM

RNA Biol 2015
26581522 Molecular mechanisms of activity and derepression of alternative lengthening of telomeres

Reddel, RR, Pickett, HA

Nat. Struct. Mol. Biol. 2015
21888887 Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes

De Marzo, AM, Kurman, RJ, Hong, SM, Maitra, A, Rakheja, D, Shih, IeM, Westra, WH, Goggins, MG, Torbenson, M, Montgomery, EA, Subhawong, AP, Argani, P, Roden, RB, Wu, TC, Meeker, AK, Netto, GJ, Li, QK, Epstein, JI, Taube, JM, Eberhart, CG, Iacobuzio-Donahue, CA, Terracciano, L, Gabrielson, E, Lotan, TL, Heaphy, CM

Am J Pathol 2011
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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