Mantenimiento de telómeros y tumores óseos
Palabras clave:
Telómero, mantenimiento, tumor, óseo, telomerasaResumen
Los telómeros son complejos de ADN y proteínas localizados en los extremos de los cromo-
somas lineales que ayudan a mantener la estabilidad genómica. En condiciones normales en
células somáticas, los telómeros se acortan con cada división celular. Cuando los telómeros
alcanzan cierta longitud, la célula entra en un periodo llamado «senescencia». Sin embargo,
algunas células pueden escapar de la senescencia; los telómeros de dichas células se siguen
acortando hasta que alcanzan una longitud en la cual la célula entra a una etapa llamada
«crisis», donde se empieza a presentar inestabilidad cromosómica, lo cual puede llevar a
muerte celular. Algunas células logran activar un mecanismo para restablecer la longitud de
los telómeros y continuar proliferando. La activación de un método de mantenimiento de
telómeros es una característica primordial de las células tumorales. Existen dos mecanismos
conocidos para el mantenimiento de telómeros: uno es la reactivación de la enzima telome-
rasa –el cual es usado por 85% de los cánceres humanos– y el segundo es la activación de la
vía alternativa de mantenimiento del largo de los telómeros (ALT) –presente en el 15% de los
tumores malignos, en su mayoría sarcomas–. El mecanismo de mantenimiento de telómeros
presente en un tumor puede servir como indicador pronóstico o de respuesta al tratamiento.
Y en un futuro, como blanco para tratamientos antineoplásicos.
##plugins.generic.pfl.publicationFactsTitle##
##plugins.generic.pfl.reviewerProfiles## N/D
##plugins.generic.pfl.authorStatements##
Indexado: {$indexList}
-
##plugins.generic.pfl.indexedList##
- ##plugins.generic.pfl.editorAndBoard##
- ##plugins.generic.pfl.profiles##
- ##plugins.generic.pfl.academicSociety##
- N/D
Para obtener más información sobre un dato, haga clic
##plugins.generic.pfl.maintainedByPKP##
Citas
Palm W, de Lange T. How shelterin protects mammalian
telomeres. Annu Rev Genet. 2008; 42: 301-334.
Compton SA, Choi JH, Cesare AJ, Ozgur S, Griffi th
JD. Xrcc3 and Nbs1 are required for the production of
extrachromosomal telomeric circles in human alternative
lengthening of telomere cells. Cancer Res. 2007; 67 (4):
-1519.
Griffi th JD, Comeau L, Rosenfi eld S, Stansel RM, Bian-
chi A, Moss H et al. Mammalian telomeres end in a large
duplex loop. Cell. 1999; 97 (4): 503-514.
De Lange T. Shelterin: the protein complex that shapes
and safeguards human telomeres. Genes Dev. 2005;
(18): 2100-2110.
Loayza D, de Lange T. POT1 as a terminal transducer
of TRF1 telomere length control. Nature. 2003; 423
(6943): 1013-1018.
Takai H, Smogorzewska A, de Lange T. DNA damage
foci at dysfunctional telomeres. Curr Biol. 2003; 13 (17):
-1556.
Denchi EL, de Lange T. Protection of telomeres through
independent control of ATM and ATR by TRF2 and
POT1. Nature. 2007; 448 (7157): 1068-1071.
Cesare AJ, Kaul Z, Cohen SB, Napier CE, Pickett
HA, Neumann AA et al. Spontaneous occurrence of
telomeric DNA damage response in the absence of
chromosome fusions. Nat Struct Mol Biol. 2009; 16 (12):
-1251.
Harley CB, Futcher AB, Greider CW. Telomeres shorten
during ageing of human fi broblasts. Nature. 1990; 345
(6274): 458-460.
Reddel RR. Alternative lengthening of telomeres,
telomerase, and cancer. Cancer Lett. 2003; 194 (2):
-162.
Wei W, Sedivy JM. Differentiation between senescence
(M1) and crisis (M2) in human fi broblast cultures. Exp
Cell Res. 1999; 253 (2): 519-522.
Shay JW, Bacchetti S. A survey of telomerase activity
in human cancer. Eur J Cancer. 1997; 33 (5): 787-791.
Shay JW, Roninson IB. Hallmarks of senescence in
carcinogenesis and cancer therapy. Oncogene. 2004;
(16): 2919-2933.
Bryan TM, Reddel RR. Telomere dynamics and telome-
rase activity in in vitro immortalised human cells. Eur J
Cancer. 1997; 33 (5): 767-773.
Zvereva MI, Shcherbakova DM, Dontsova OA. Telo-
merase: structure, functions, and activity regulation.
Biochemistry (Mosc). 2010; 75 (13): 1563-1583.
Greider CW, Blackburn EH. The telomere terminal trans-
ferase of tetrahymena is a ribonucleoprotein enzyme
with two kinds of primer specifi city. Cell. 1987; 51 (6):
-898.
Hsu M, Yu EY, Singh SM, Lue NF. Mutual dependence
of Candida albicans Est1p and Est3p in telomerase
assembly and activation. Eukaryot Cell. 2007; 6 (8):
-1338.
Mitchell JR, Collins K. Human telomerase activation re-
quires two independent interactions between telomerase
RNA and telomerase reverse transcriptase. Mol Cell.
; 6 (2): 361-371.
Skvortsov DA, Zvereva ME, Shpanchenko OV, Dontsova
OA. Assays for detection of telomerase activity. Acta
Naturae. 2011; 3 (1): 48-68.
Cesare AJ, Reddel RR. Alternative lengthening of telo-
meres: models, mechanisms and implications. Nat Rev
Genet. 2010; 11 (5): 319-330.
Varley H, Pickett HA, Foxon JL, Reddel RR, Royle NJ.
Molecular characterization of inter-telomere and intra-
telomere mutations in human ALT cells. Nat Genet.
; 30 (3): 301-305.
Jiang WQ, Zhong ZH, Henson JD, Neumann AA, Chang
AC, Reddel RR, et al. Suppression of alternative lengthe-
ning of telomeres by Sp100-mediated sequestration of
the MRE11/RAD50/NBS1 complex. Mol Cell Biol. 2005;
(7): 2708-2721.
Nabetani A, Ishikawa F. Unusual telomeric DNAs in
human telomerase-negative immortalized cells. Mol Cell
Biol. 2009; 29 (3): 703-713.
Yeager TR, Neumann AA, Englezou A, Huschtscha LI,
Noble JR, Reddel RR et al. Telomerase-negative immor-
talized human cells contain a novel type of promyelocytic
leukemia (PML) body. Cancer Res. 1999; 59 (17): 4175-
Draskovic I, Arnoult N, Steiner V, Bacchetti S, Lomonte
P, Londono-Vallejo A et al. Probing PML body function
in ALT cells reveals spatiotemporal requirements for
telomere recombination. Proc Natl Acad Sci U S A.
; 106 (37): 15726-15731.
Pickett HA, Cesare AJ, Johnston RL, Neumann AA,
Reddel RR. Control of telomere length by a trimming
mechanism that involves generation of t-circles. EMBO
J. 2009; 28 (7): 799-809.
Fasching CL, Neumann AA, Muntoni A, Yeager TR,
Reddel RR. DNA damage induces alternative lengthe-
ning of telomeres (ALT) associated promyelocytic
leukemia bodies that preferentially associate with linear
telomeric DNA. Cancer Res. 2007; 67 (15): 7072-7077.
Jeyapalan JN, Varley H, Foxon JL, Pollock RE, Jeffreys
AJ, Henson JD et al. Activation of the ALT pathway for
telomere maintenance can affect other sequences in
the human genome. Hum Mol Genet. 2005; 14 (13):
-1794.
Londono-Vallejo JA, Der-Sarkissian H, Cazes L, Bac-
chetti S, Reddel RR. Alternative lengthening of telome-
res is characterized by high rates of telomeric exchange.
Cancer Res. 2004; 64 (7): 2324-2327.
Maringele L, Lydall D. EXO1 plays a role in generating
type I and type II survivors in budding yeast. Genetics.
; 166 (4): 1641-1649.
Chen Q, Ijpma A, Greider CW. Two survivor pathways
that allow growth in the absence of telomerase are
generated by distinct telomere recombination events.
Mol Cell Biol. 2001; 21 (5): 1819-1827.
Bonetti D, Martina M, Clerici M, Lucchini G, Longhese
MP. Multiple pathways regulate 3’ overhang generation
at S. cerevisiae telomeres. Mol Cell. 2009; 35 (1): 70-81.
Matsuo T, Shimose S, Kubo T, Fujimori J, Yasunaga
Y, Ochi M. Telomeres and telomerase in sarcomas.
Anticancer Res. 2009; 29 (10): 3833-3836.
Ohali A, Avigad S, Cohen IJ, Meller I, Kollender Y, Issa-
kov J et al. Association between telomerase activity and
outcome in patients with non metastatic Ewing family of
tumors. J Clin Oncol. 2003; 21 (20): 3836-3843.
Terasaki T, Kyo S, Takakura M, Maida Y, Tsuchiya
H, Tomita K et al. Analysis of telomerase activity and
telomere length in bone and soft tissue tumors. Oncol
Rep. 2004; 11 (6): 1307-1311.
Ulaner GA, Hoffman AR, Otero J, Huang HY, Zhao Z,
Mazumdar M et al. Divergent patterns of telomere main-
tenance mechanisms among human sarcomas: sharply
contrasting prevalence of the alternative lengthening of
telomeres mechanism in Ewing’s sarcomas and osteo-
sarcomas. Genes Chromosomes Cancer. 2004; 41 (2):
-162.
Matsuo T, Hiyama E, Sugita T, Shimose S, Kubo T,
Mochizuki Y et al. Telomerase activity in giant cell tumors
of bone. Ann Surg Oncol. 2007; 14 (10): 2896-2902.
Forsyth RG, De Boeck G, Bekaert S, De Meyer T, Tami-
niau AH, Uyttendaele D et al. Telomere biology in giant
cell tumour of bone. J Pathol. 2008; 214 (5): 555-563.
Gorunova L, Vult von Steyern F, Storlazzi CT, Bjerke-
hagen B, Folleras G, Heim S et al. Cytogenetic analysis
of 101 giant cell tumors of bone: nonrandom patterns of
telomeric associations and other structural aberrations.
Genes Chromosomes Cancer. 2009; 48 (7): 583-602.
Letsolo BT, Rowson J, Baird DM. Fusion of short te-
lomeres in human cells is characterized by extensive
deletion and microhomology, and can result in complex
rearrangements. Nucleic Acids Res. 2010; 38 (6): 1841-
Ulaner GA, Huang HY, Otero J, Zhao Z, Ben-Porat L,
Satagopan JM et al. Absence of a telomere maintenance
mechanism as a favorable prognostic factor in patients
with osteosarcoma. Cancer Res. 2003; 63 (8): 1759-
Sanders RP, Drissi R, Billups CA, Daw NC, Valentine
MB, Dome JS. Telomerase expression predicts unfavo-
rable outcome in osteosarcoma. J Clin Oncol. 2004; 22
(18): 3790-3797.
Sotillo-Pineiro E, Sierrasesumaga L, Patinno-Garcia A.
Telomerase activity and telomere length in primary and
metastatic tumors from pediatric bone cancer patients.
Pediatr Res. 2004; 55 (2): 231-235.
Gocha AR, Nuovo G, Iwenofu OH, Groden J. Human
sarcomas are mosaic for telomerase-dependent and
telomerase-independent telomere maintenance mecha-
nisms: Implications for telomere-based therapies. Am J
Pathol. 2013; 182 (1): 41-48.
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2026 Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
© Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra under a Creative Commons Attribution 4.0 International (CC BY 4.0) license which allows to reproduce and modify the content if appropiate recognition to the original source is given.
