Búsqueda de nuevos biomarcadores genéticos en gliomas de alto grado

Autores/as

DOI:

https://doi.org/10.17533/udea.acbi.v41n111a01

Palabras clave:

diagnóstico, genética, pronóstico, reparación del ADN, sangre, valor predictivo de las pruebas

Resumen


Los gliomas de alto grado son los tumores cerebrales más comunes dentro de las neoplasias del sistema nervioso central (SNC); presentan una sobrevida media de sólo 18 meses, debido principalmente a su resistencia a las diferentes estrategias terapéuticas. A la fecha, el único tratamiento que ha logrado aumentar algunos meses la sobrevida de los pacientes con estos gliomas es el protocolo diseñado por Stupp et al. (2005), que consta de una cirugía junto con temozolamida (TMZ) y radioterapia (RT) adyuvante. Sin embargo, aunque prolonga hasta 18 meses la vida de los pacientes, aún carece de valor pronóstico sensible y/o específico.

Hasta ahora sólo existen tres marcadores moleculares de relevancia clínica para esta enfermedad; sin embargo, el Instituto Nacional de Salud de los Estados Unidos detectó un grupo de individuos (“respondedores excepcionales”) que parecen tener una supervivencia más larga asociada a la hipermetilación del promotor del gen MGMT. Estudios recientes sugieren que en los “respondedores excepcionales” hay otros factores genéticos no descritos involucrados en la reparación de daños en el ADN.

En esta revisión se sugiere emplear la reparación del ADN como un biomarcador cuando los pacientes con gliomas de alto grado son tratados con los genotóxicos TMZ y RT. Además, se describen con detalle tres técnicas que permiten cuantificar la inestabilidad genética de estos pacientes: la detección de Micronúcleos (MN) en linfocitos de sangre periférica mediante el método de Fenech, la detección de MN en reticulocitos de sangre periférica mediante citometría de flujo, y el Intercambio de Cromátidas Hermanas (ICH).

|Resumen
= 348 veces | PDF
= 284 veces| | HTML
= 17 veces| | HTML1
= 0 veces|

Descargas

Los datos de descargas todavía no están disponibles.

Biografía del autor/a

Lina Marcela Barrera-Arenas, Corporación Universitaria Remington.

Grupo Genética, Regeneración y Cáncer (GRC), Instituto de Biología, Sede de Investigación Universitaria, Universidad de Antioquia, Medellín, Colombia

Julieth Restrepo, Corporación Universitaria Remington.

Grupo de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Corporación Universitaria Remington, Medellín, Colombia

León Darío Ortíz, Universidad CES, Medellín

Instituto de Cancerología-Clínica Las Américas, Medellín, Colombia

Mauricio Camargo, Universidad de Antioquia.

Grupo de Ciencias Farmacológicas y Ciencias Básicas, Facultad de Ciencias de la Salud, Área farmacogenómica, CES, Medellín, Colombia.

Citas

Alentorn A, Duran-Peña A, Pingle SC, Piccioni DE, Idbaih A, Kesari S. 2015. Molecular profiling of gliomas: potential therapeutic implications. Expert Rev Anticancer Ther. 15(8):955–962. doi:10.1586/14737140.2015.1062368.

Araldi RP, de Melo TC, Mendes TB, de Sá Júnior PL, Nozima BHN, Ito ET, de Carvalho RF, de Souza EB, de Cassia Stocco R. 2015. Using the comet and micronucleus assays for genotoxicity studies: A review. Biomed Pharmacother. 72:74–82. doi:10.1016/j.biopha.2015.04.004.

Balaña C, Cardona AF. 2008. Bevacizumab en gliomas de alto grado recurrentes: reporte de un caso y revisión de la literatura.

Balmus G, Karp NA, Ng BL, Jackson SP, Adams DJ, McIntyre RE. 2015. A high-throughput in vivo micronucleus assay for genome instability screening in mice. Nat Protoc. 10(1):205–215. doi:10.1038/nprot.2015.010. [accessed 2019 May 15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806852/.

Banerjee A, Benedict WF. 1979. Production of sister chromatid exchanges by various cancer chemotherapeutic agents. Cancer Res. 39(3):797–799.

Barrera LM, Ortiz LD, Grisales H, Rojas M, Camargo M. 2018. Citometría de flujo en reticulocitos de sangre periférica como indicador de inestabilidad cromosómica en pacientes con gliomas de alto grado. 1. 38(3):379–387. doi:10.7705/biomedica.v38i4.3882. [accessed 2019 May 16]. https://www.revistabiomedica.org/index.php/biomedica/article/view/3882.

Begg AC, Stewart FA, Vens C. 2011. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 11(4):239–253. doi:10.1038/nrc3007.

Bleeker FE, Molenaar RJ, Leenstra S. 2012. Recent advances in the molecular understanding of glioblastoma. J Neurooncol. 108(1):11–27. doi:10.1007/s11060-011-0793-0. [accessed 2019 Nov 5]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337398/.

Bloching M, Hofmann A, Lautenschläger C, Berghaus A, Grummt T. 2000. Exfoliative cytology of normal buccal to predict the relative risk of cancer in the upper aerodigestive tract using the MN-assay. Oral oncology. 36:550–5. doi:10.1016/S1368-8375(00)00051-8.

Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, et al. 2007. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 28(3):625–631. doi:10.1093/carcin/bgl177.

Brandes AA, Nicolardi L, Tosoni A, Gardiman M, Iuzzolino P, Ghimenton C, Reni M, Rotilio A, Sotti G, Ermani M. 2006. Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma. Neuro-oncol. 8(3):253–260. doi:10.1215/15228517-2006-005. [accessed 2019 May 15].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871946/.

Cancer Genome Atlas Research Network, Brat DJ, Verhaak RGW, Aldape KD, Yung WKA, Salama SR, Cooper LAD, Rheinbay E, Miller CR, Vitucci M, et al. 2015. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med. 372(26):2481–2498. doi:10.1056/NEJMoa1402121.

Chang P, Li Y, Li D. 2011. Micronuclei levels in peripheral blood lymphocytes as a potential biomarker for pancreatic cancer risk. Carcinogenesis. 32(2):210–215. doi:10.1093/carcin/bgq247.

Chen Y, Tsai Y, Nowak I, Wang N, Hyrien O, Wilkins R, Ferrarotto C, Sun H, Dertinger SD. 2010. Validating high-throughput micronucleus analysis of peripheral reticulocytes for radiation biodosimetry: benchmark against dicentric and CBMN assays in a mouse model. Health Phys. 98(2):218–227. doi:10.1097/HP.0b013e3181abaae5.

Cohen AL, Colman H. 2015. Glioma biology and molecular markers. Cancer Treat Res. 163:15–30. doi:10.1007/978-3-319-12048-5_2.

Dertinger SD, Miller RK, Brewer K, Smudzin T, Torous DK, Roberts DJ, Avlasevich SL, Bryce SM, Sugunan S, Chen Y. 2007a. Automated Human Blood Micronucleated Reticulocyte Measurements for Rapid Assessment of Chromosomal Damage. Mutat Res. 626(1–2):111–119. doi:10.1016/j.mrgentox.2006.09.003. [accessed 2019 May 15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796663/.

Dertinger SD, Miller RK, Brewer K, Smudzin T, Torous DK, Roberts DJ, Avlasevich SL, Bryce SM, Sugunan S, Chen Y. 2007b. Automated Human Blood Micronucleated Reticulocyte Measurements for Rapid Assessment of Chromosomal Damage. Mutat Res. 626(1–2):111–119. doi:10.1016/j.mrgentox.2006.09.003. [accessed 2019 May 15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796663/.

Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV, et al. 2015. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 372(26):2499–2508. doi:10.1056/NEJMoa1407279.

Felsberg J, Rapp M, Loeser S, Fimmers R, Stummer W, Goeppert M, Steiger H-J, Friedensdorf B, Reifenberger G, Sabel MC. 2009. Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res. 15(21):6683–6693. doi:10.1158/1078-0432.CCR-08-2801.

Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. 1999. The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res. 428(1–2):271–283.

Fenech M, Kirsch-Volders M, Natarajan A, Surrallés J, Crott JW, Parry J, Norppa H, Eastmond DA, Tucker JD, Thomas P. 2011. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136(5):E359-386. doi:10.1002/ijc.29210.

Galia A, Calogero AE, Condorelli R, Fraggetta F, La Corte A, Ridolfo F, Bosco P, Castiglione R, Salemi M. 2012. PARP-1 protein expression in glioblastoma multiforme. Eur J Histochem. 56(1):e9. doi:10.4081/ejh.2012.e9.

Gil Del Alcazar CR, Todorova PK, Habib AA, Mukherjee B, Burma S. 2016. Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma. Mol Cancer Res. 14(10):928–940. doi:10.1158/1541-7786.MCR-16-0125.

Guan X, Vengoechea J, Zheng S, Sloan AE, Chen Y, Brat DJ, O’Neill BP, de Groot J, Yust-Katz S, Yung W-KA, et al. 2014. Molecular subtypes of glioblastoma are relevant to lower grade glioma. PLoS ONE. 9(3):e91216. doi:10.1371/journal.pone.0091216.

Haglund U, Hayder S, Zech L. 1980. Sister chromatid exchanges and chromosome aberrations in children after treatment for malignant lymphoma. Cancer Res. 40(12):4786–4790.

Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell. 144(5):646–674. doi:10.1016/j.cell.2011.02.013.

Hartmann C, Hentschel B, Tatagiba M, Schramm J, Schnell O, Seidel C, Stein R, Reifenberger G, Pietsch T, von Deimling A, et al. 2011. Molecular markers in low-grade gliomas: predictive or prognostic? Clin Cancer Res. 17(13):4588–4599. doi:10.1158/1078-0432.CCR-10-3194.

International agency of research on cancer. 2018. All cancers. World health organization. [accessed 2019 Nov 5]. https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf.

Javle M, Curtin NJ. 2011. The role of PARP in DNA repair and its therapeutic exploitation. Br J Cancer. 105(8):1114–1122. doi:10.1038/bjc.2011.382.

Kaina B. 2004. Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: a long road traveled and still a far way to go. Cytogenet Genome Res. 104(1–4):77–86. doi:10.1159/000077469.

Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, Sabel M, Steinbach JP, Heese O, Reifenberger G, et al. 2007. Long-term survival with glioblastoma multiforme. Brain. 130(Pt 10):2596–2606. doi:10.1093/brain/awm204.

Lim YC, Roberts TL, Day BW, Harding A, Kozlov S, Kijas AW, Ensbey KS, Walker DG, Lavin MF. 2012. A role for homologous recombination and abnormal cell-cycle progression in radioresistance of glioma-initiating cells. Mol Cancer Ther. 11(9):1863–1872. doi:10.1158/1535-7163.MCT-11-1044.

Lim YC, Roberts TL, Day BW, Stringer BW, Kozlov S, Fazry S, Bruce ZC, Ensbey KS, Walker DG, Boyd AW, et al. 2014a. Increased sensitivity to ionizing radiation by targeting the homologous recombination pathway in glioma initiating cells. Mol Oncol. 8(8):1603–1615. doi:10.1016/j.molonc.2014.06.012. [accessed 2019 May 16]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528585/.

Lim YC, Roberts TL, Day BW, Stringer BW, Kozlov S, Fazry S, Bruce ZC, Ensbey KS, Walker DG, Boyd AW, et al. 2014b. Increased sensitivity to ionizing radiation by targeting the homologous recombination pathway in glioma initiating cells. Mol Oncol. 8(8):1603–1615. doi:10.1016/j.molonc.2014.06.012.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. 2007. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathol. 114(2):97–109. doi:10.1007/s00401-007-0243-4. [accessed 2019 Sep 28]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1929165/.

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. 2016. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 131(6):803–820. doi:10.1007/s00401-016-1545-1.

Marumoto T, Saya H. 2012. Molecular biology of glioma. Adv Exp Med Biol. 746:2–11. doi:10.1007/978-1-4614-3146-6_1.

Mellai M, Caldera V, Annovazzi L, Chiò A, Lanotte M, Cassoni P, Finocchiaro G, Schiffer D. 2009. MGMT promoter hypermethylation in a series of 104 glioblastomas. Cancer Genomics Proteomics. 6(4):219–227.

Minniti G, Enrici RM. 2014. Radiation therapy for older adults with glioblastoma: radical treatment, palliative treatment, or no treatment at all? J Neurooncol. 120(2):225–233. doi:10.1007/s11060-014-1566-3.

Mittal S, Pradhan S, Srivastava T. 2015. Recent advances in targeted therapy for glioblastoma. Expert Rev Neurother. 15(8):935–946. doi:10.1586/14737175.2015.1061934.

Mullard A. 2014. Learning from exceptional drug responders. Nat Rev Drug Discov. 13(6):401–402. doi:10.1038/nrd4338.

Murgia E, Ballardin M, Bonassi S, Rossi AM, Barale R. 2008. Validation of micronuclei frequency in peripheral blood lymphocytes as early cancer risk biomarker in a nested case-control study. Mutat Res. 639(1–2):27–34. doi:10.1016/j.mrfmmm.2007.10.010.

Olar A, Sulman EP. 2015. Molecular Markers in Low Grade Glioma – Toward Tumor Reclassification. Semin Radiat Oncol. 25(3):155–163. doi:10.1016/j.semradonc.2015.02.006. [accessed 2019 Nov 5]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500036/.

Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, et al. 2014. The epidemiology of glioma in adults: a “state of the science” review. Neuro-oncology. 16(7):896–913. doi:10.1093/neuonc/nou087.

Pace A, Dirven L, Koekkoek JAF, Golla H, Fleming J, Rudà R, Marosi C, Le Rhun E, Grant R, Oliver K, et al. 2017. European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma. Lancet Oncol. 18(6):e330–e340. doi:10.1016/S1470-2045(17)30345-5.

Pardo C, de Vries E. 2017. Supervivencia global de pacientes con cáncer en el Instituto Nacional de Cancerología (INC). Revista Colombiana de Cancerología. 21(1):12–18. doi:10.1016/j.rccan.2017.01.003. [accessed 2019 Sep 28]. http://www.sciencedirect.com/science/article/pii/S0123901517300082.

Piñeros M, Sierra MS, Izarzugaza MI, Forman D. 2016. Descriptive epidemiology of brain and central nervous system cancers in Central and South America. Cancer Epidemiol. 44 Suppl 1:S141–S149. doi:10.1016/j.canep.2016.04.007.

Quiros S, Roos WP, Kaina B. 2011. Rad51 and BRCA2--New molecular targets for sensitizing glioma cells to alkylating anticancer drugs. PLoS ONE. 6(11):e27183. doi:10.1371/journal.pone.0027183.

Ranjit M, Motomura K, Ohka F, Wakabayashi T, Natsume A. 2015. Applicable advances in the molecular pathology of glioblastoma. Brain Tumor Pathol. 32(3):153–162. doi:10.1007/s10014-015-0224-6.

Roos WP, Nikolova T, Quiros S, Naumann SC, Kiedron O, Zdzienicka MZ, Kaina B. 2009. Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations by a process leading to SCEs. DNA Repair (Amst). 8(1):72–86. doi:10.1016/j.dnarep.2008.09.003.

Schmid W. 1975. The micronucleus test. Mutat Res. 31(1):9–15.

Sheridan C. 2014. Cancer centers zero in on exceptional responders. Nat Biotechnol. 32(8):703–704. doi:10.1038/nbt0814-703.

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJB, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al. 2009. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 10(5):459–466. doi:10.1016/S1470-2045(09)70025-7.

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. 2005. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352(10):987–996. doi:10.1056/NEJMoa043330.

Takahashi Y, Nakamura H, Makino K, Hide T, Muta D, Kamada H, Kuratsu J-I. 2013. Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients. World J Surg Oncol. 11:284. doi:10.1186/1477-7819-11-284.

Tokuda K, Bodell WJ. 1988. Cytotoxicity and induction of sister chromatid exchanges in human and rodent brain tumor cells treated with alkylating chemotherapeutic agents. Cancer Res. 48(11):3100–3105.

Wang J, Su H, Zhao H, Chen Z, To ST. 2015. Progress in the application of molecular biomarkers in gliomas. Biochem Biophys Res Commun. 465(1):1–4. doi:10.1016/j.bbrc.2015.07.148.

Wilson DM, Thompson LH. 2007. Molecular mechanisms of sister-chromatid exchange. Mutat Res. 616(1–2):11–23. doi:10.1016/j.mrfmmm.2006.11.017.

Descargas

Publicado

2020-02-26

Cómo citar

Barrera Arenas, L. M., Restrepo Atehortúa, J., Ortíz, L. D., & Camargo Guerrero, M. (2020). Búsqueda de nuevos biomarcadores genéticos en gliomas de alto grado. Actualidades Biológicas, 41(111), 01–9. https://doi.org/10.17533/udea.acbi.v41n111a01

Número

Sección

Artículos de revisión