Search for new genetic biomarkers in high-grade gliomas
DOI:
https://doi.org/10.17533/udea.acbi.v41n111a01Keywords:
diagnosis, genetics, prognosis, DNA repair, blood, predictive value of the testsAbstract
High-grade gliomas are the most common brain tumors within central nervous system (CNS) neoplasms; they have an average survival of only 18 months, mainly due to their resistance to different therapeutic strategies. To date, the only treatment that has managed to improve in some months the survival of patients with these gliomas is the protocol designed by Stupp et al. (2005), which consists of surgery paired with adjuvant temozolamide (TMZ), and radiotherapy (RT). However, despite prolonging the life of patients up to 18 months, it still lacks a sensitive and/or specific prognostic value.
So far, there are only three molecular markers of clinical relevance for this disease; however, the National Institute of Health of the United States, detected a small group of individuals ("exceptional responders") that seem to have a longer survival associated with hypermethylation of the promoter of gene MGMT. Recent studies suggest that in “exceptional responders” there are other genetic factors not yet described involved in DNA damage repair.
In this review the use of DNA repair as a biomarker is suggested when patients with high-grade gliomas are treated with genotoxics TMZ and RT. Furthermore, three techniques that allow quantification of the genetic instability of these patients are detailed: detection of Micronuclei (MN) in peripheral blood lymphocytes by Fenech method, detection of MN in peripheral blood reticulocytes by flow cytometry, and Sister Chromatid Exchange (SCE).
Downloads
References
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.
Published
How to Cite
Issue
Section
License
Copyright (c) 2020 Actualidades Biológicas
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The authors exclusively authorize the Actualidades Biológicas journal to edit and publish the submitted manuscript if its publication is recommended and accepted, without this representing any cost to the Journal or the University of Antioquia.
All the ideas and opinions contained in the articles are sole responsibility of the authors. The total content of the issues or supplements of the journal is protected under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, so they cannot be used for commercial purposes, but for educational purposes. However, please mention the Actualidades Biológicas journal as a source and send a copy of the publication in which the content was reproduced.
