Diseases of Telomere Maintenance

Stable Identifier
Homo sapiens
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Somatic mutations or rearrangements in genes involved in telomere maintenance enable immortalization of cancer cells either through upregulation of telomerase activity or through activation of alternative lengthening of telomeres (ALT) (Killela et al. 2013, reviewed by Gocha et al. 2013, Pickett and Reddel 2015, Amorim et al. 2016, Yuan et al. 2019). Germline mutations in telomere maintenance genes lead to telomere syndromes, such as dyskeratosis congenita (DC) and Hoyeraal-Hreidarsson (HH) syndrome, characterized by impaired ability to maintain telomere lengths during growth and development, leading to abnormally short telomere lengths and genomic instability that affects multiple organs and is associated with increased risk of certain cancers (reviewed by Sarek et al. 2015).
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
31285550 Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players

Larsson, C, Xu, D, Yuan, X

Oncogene 2019
26581521 Molecular basis of telomere dysfunction in human genetic diseases

Marzec, P, Boulton, SJ, Margalef, P, Sarek, G

Nat. Struct. Mol. Biol. 2015
23530248 TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal

Mandahl, N, He, Y, Hruban, RH, Diaz, LA, McLendon, RE, Zhang, M, Wood, LD, Papadopoulos, N, Schiffman, M, Gallia, GL, Torbenson, MS, Bettegowda, C, He, TC, Grollman, AP, Reitman, ZJ, Kinzler, KW, Vogelstein, B, Agrawal, N, Giovanella, BC, Rosenquist, TA, Wang, TL, Velculescu, VE, Shih, IeM, Yan, H, Friedman, AH, Riggins, GJ, Friedman, H, Jallo, GI, Meeker, AK, Rasheed, BA, Netto, GJ, Theodorescu, D, Killela, PJ, Wentzensen, N, Jiao, Y, Bigner, DD, Mertens, F

Proc. Natl. Acad. Sci. U.S.A. 2013
23219603 Alternative mechanisms of telomere lengthening: permissive mutations, DNA repair proteins and tumorigenic progression

Groden, J, Gocha, AR, Harris, J

Mutat. Res. 2013
26581522 Molecular mechanisms of activity and derepression of alternative lengthening of telomeres

Reddel, RR, Pickett, HA

Nat. Struct. Mol. Biol. 2015
Name Identifier Synonyms
genetic disease DOID:630
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