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Age-associated brain regions in gliomas: a volumetric analysis

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Abstract

Both age of patients and tumor location are associated with tumor origin, genetic characteristics, and prognosis. The objective of this study was to investigate the relationship between tumor location and age at diagnosis in a large cohort of patients with a primary diagnosis of glioma. We consecutively enrolled a cohort of 200 adults with glioblastoma and another cohort of 200 adults with diffuse low-grade gliomas. The magnetic resonance images of all tumors were manually segmented and then registered to a standard brain space. By using voxel-by-voxel regression analysis, specific brains regions associated with advanced age at tumor diagnosis were localized. In the low-grade gliomas cohort, the brain regions associated with advanced age at tumor diagnosis were mainly located in the right middle frontal region, while a region in the left temporal lobe, particularly at the subgranular zone, was associated with lower age at tumor diagnosis. In the glioblastoma cohort, the brain regions associated with advanced age at tumor diagnosis were mainly located in the temporal lobe, particularly at the posterior region of the subventricular zones. A region in the left inferior frontal region was associated with lower age at tumor diagnosis. Significant differences in the age of patients were found between tumors located in the identified regions and those located elsewhere in both cohorts. The current study demonstrated the correlation between tumor location and age at diagnosis, which implies differences in the origin of gliomas in young and older patients.

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References

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996

    Article  CAS  PubMed  Google Scholar 

  2. 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

    Article  PubMed Central  PubMed  Google Scholar 

  3. Bauman G, Fisher B, Watling C, Cairncross JG, Macdonald D (2009) Adult supratentorial low-grade glioma: long-term experience at a single institution. Int J Radiat Oncol Biol Phys 75(5):1401–1407

    Article  PubMed  Google Scholar 

  4. Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64(6):479–489

    CAS  PubMed  Google Scholar 

  5. Porter KR, McCarthy BJ, Freels S, Kim Y, Davis FG (2010) Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology. Neuro Oncol 12(6):520–527

    Article  PubMed Central  PubMed  Google Scholar 

  6. Barker FG 2nd, Chang SM, Larson DA, Sneed PK, Wara WM, Wilson CB, Prados MD (2001) Age and radiation response in glioblastoma multiforme. Neurosurgery 49(6):1288–1297 (discussion 1297–1288)

    Article  PubMed  Google Scholar 

  7. Simpson JR, Horton J, Scott C, Curran WJ, Rubin P, Fischbach J, Isaacson S, Rotman M, Asbell SO, Nelson JS et al (1993) Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 26(2):239–244

    Article  CAS  PubMed  Google Scholar 

  8. Karim AB, Afra D, Cornu P, Bleehan N, Schraub S, De Witte O, Darcel F, Stenning S, Pierart M, Van Glabbeke M (2002) Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys 52(2):316–324

    Article  PubMed  Google Scholar 

  9. Karim AB, Maat B, Hatlevoll R, Menten J, Rutten EH, Thomas DG, Mascarenhas F, Horiot JC, Parvinen LM, van Reijn M, Jager JJ, Fabrini MG, van Alphen AM, Hamers HP, Gaspar L, Noordman E, Pierart M, van Glabbeke M (1996) A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844. Int J Radiat Oncol Biol Phys 36(3):549–556

    Article  CAS  PubMed  Google Scholar 

  10. Fisher BJ, Naumova E, Leighton CC, Naumov GN, Kerklviet N, Fortin D, Macdonald DR, Cairncross JG, Bauman GS, Stitt L (2002) Ki-67: a prognostic factor for low-grade glioma? Int J Radiat Oncol Biol Phys 52(4):996–1001

    Article  PubMed  Google Scholar 

  11. Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JW, Wesseling P, Reifenberger G, von Deimling A (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1010 diffuse gliomas. Acta Neuropathol 118(4):469–474

    Article  PubMed  Google Scholar 

  12. Mikheev AM, Stoll EA, Mikheeva SA, Maxwell JP, Jankowski PP, Ray S, Uo T, Morrison RS, Horner PJ, Rostomily RC (2009) A syngeneic glioma model to assess the impact of neural progenitor target cell age on tumor malignancy. Aging Cell 8(4):499–501

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16(6):2027–2033

    CAS  PubMed  Google Scholar 

  14. Wrensch M, Minn Y, Chew T, Bondy M, Berger MS (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 4(4):278–299

    PubMed Central  PubMed  Google Scholar 

  15. Jeremic B, Grujicic D, Antunovic V, Djuric L, Stojanovic M, Shibamoto Y (1994) Influence of extent of surgery and tumor location on treatment outcome of patients with glioblastoma multiforme treated with combined modality approach. J Neurooncol 21(2):177–185

    Article  CAS  PubMed  Google Scholar 

  16. Duffau H, Capelle L (2004) Preferential brain locations of low-grade gliomas. Cancer 100(12):2622–2626

    Article  PubMed  Google Scholar 

  17. Lai A, Kharbanda S, Pope WB, Tran A, Solis OE, Peale F, Forrest WF, Pujara K, Carrillo JA, Pandita A, Ellingson BM, Bowers CW, Soriano RH, Schmidt NO, Mohan S, Yong WH, Seshagiri S, Modrusan Z, Jiang Z, Aldape KD, Mischel PS, Liau LM, Escovedo CJ, Chen W, Nghiemphu PL, James CD, Prados MD, Westphal M, Lamszus K, Cloughesy T, Phillips HS (2011) Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. J Clin Oncol 29(34):4482–4490

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Stockhammer F, Misch M, Helms HJ, Lengler U, Prall F, von Deimling A, Hartmann C (2012) IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom. Seizure 21(3):194–197

    Article  PubMed  Google Scholar 

  19. Ren X, Cui X, Lin S, Wang J, Jiang Z, Sui D, Li J, Wang Z (2012) Co-deletion of chromosome 1p/19q and IDH1/2 mutation in glioma subsets of brain tumors in Chinese patients. PLoS ONE 7(3):e32764

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Wang Y, Zhang T, Li S, Fan X, Ma J, Wang L, Jiang T (2015) Anatomical localization of isocitrate dehydrogenase 1 mutation: a voxel-based radiographic study of 146 low-grade gliomas. Eur J Neurol 22(2):348–354

    Article  CAS  PubMed  Google Scholar 

  21. Ellingson BM, Cloughesy TF, Pope WB, Zaw TM, Phillips H, Lalezari S, Nghiemphu PL, Ibrahim H, Naeini KM, Harris RJ, Lai A (2012) Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas. Neuroimage 59(2):908–916

    Article  CAS  PubMed  Google Scholar 

  22. Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Ozduman K, Avsar T, Li J, Murray PB, Henegariu O, Yilmaz S, Gunel JM, Carrion-Grant G, Yilmaz B, Grady C, Tanrikulu B, Bakircioglu M, Kaymakcalan H, Caglayan AO, Sencar L, Ceyhun E, Atik AF, Bayri Y, Bai H, Kolb LE, Hebert RM, Omay SB, Mishra-Gorur K, Choi M, Overton JD, Holland EC, Mane S, State MW, Bilguvar K, Baehring JM, Gutin PH, Piepmeier JM, Vortmeyer A, Brennan CW, Pamir MN, Kilic T, Lifton RP, Noonan JP, Yasuno K, Gunel M (2013) Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science 339(6123):1077–1080

    Article  CAS  PubMed  Google Scholar 

  23. Zlatescu MC, TehraniYazdi A, Sasaki H, Megyesi JF, Betensky RA, Louis DN, Cairncross JG (2001) Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms. Cancer Res 61(18):6713–6715

    CAS  PubMed  Google Scholar 

  24. Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, Dronkers NF (2003) Voxel-based lesion-symptom mapping. Nat Neurosci 6(5):448–450

    CAS  PubMed  Google Scholar 

  25. Verdon V, Schwartz S, Lovblad KO, Hauert CA, Vuilleumier P (2010) Neuroanatomy of hemispatial neglect and its functional components: a study using voxel-based lesion-symptom mapping. Brain 133(Pt 3):880–894

    Article  PubMed  Google Scholar 

  26. Glascher J, Adolphs R, Damasio H, Bechara A, Rudrauf D, Calamia M, Paul LK, Tranel D (2012) Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex. Proc Natl Acad Sci USA 109(36):14681–14686

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Rousseaux M, Honore J, Vuilleumier P, Saj A (2013) Neuroanatomy of space, body, and posture perception in patients with right hemisphere stroke. Neurology 81(15):1291–1297

    Article  PubMed  Google Scholar 

  28. Barajas RF Jr, Phillips JJ, Parvataneni R, Molinaro A, Essock-Burns E, Bourne G, Parsa AT, Aghi MK, McDermott MW, Berger MS, Cha S, Chang SM, Nelson SJ (2012) Regional variation in histopathologic features of tumor specimens from treatment-naive glioblastoma correlates with anatomic and physiologic MR Imaging. Neuro Oncol 14(7):942–954

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Kelly PJ, Daumas-Duport C, Kispert DB, Kall BA, Scheithauer BW, Illig JJ (1987) Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. J Neurosurg 66(6):865–874

    Article  CAS  PubMed  Google Scholar 

  30. Wang Y, Qian T, You G, Peng X, Chen C, You Y, Yao K, Wu C, Ma J, Sha Z, Wang S, Jiang T (2015) Localizing seizure-susceptible brain regions associated with low-grade gliomas using voxel-based lesion-symptom mapping. Neuro Oncol 17(2):282–288

    Article  PubMed  Google Scholar 

  31. Kimberg DY, Coslett HB, Schwartz MF (2007) Power in voxel-based lesion-symptom mapping. J Cogn Neurosci 19(7):1067–1080

    Article  PubMed  Google Scholar 

  32. Medina J, Kimberg DY, Chatterjee A, Coslett HB (2010) Inappropriate usage of the Brunner–Munzel test in recent voxel-based lesion-symptom mapping studies. Neuropsychologia 48(1):341–343

    Article  PubMed Central  PubMed  Google Scholar 

  33. Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R, Benner A, Hielscher T, Milde T, Remke M, Jones DT, Northcott PA, Garzia L, Bertrand KC, Wittmann A, Yao Y, Roberts SS, Massimi L, Van Meter T, Weiss WA, Gupta N, Grajkowska W, Lach B, Cho YJ, von Deimling A, Kulozik AE, Witt O, Bader GD, Hawkins CE, Tabori U, Guha A, Rutka JT, Lichter P, Korshunov A, Taylor MD, Pfister SM (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20(2):143–157

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tonjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY, Fontebasso AM, Ryzhova M, Albrecht S, Jacob K, Wolter M, Ebinger M, Schuhmann MU, van Meter T, Fruhwald MC, Hauch H, Pekrun A, Radlwimmer B, Niehues T, von Komorowski G, Durken M, Kulozik AE, Madden J, Donson A, Foreman NK, Drissi R, Fouladi M, Scheurlen W, von Deimling A, Monoranu C, Roggendorf W, Herold-Mende C, Unterberg A, Kramm CM, Felsberg J, Hartmann C, Wiestler B, Wick W, Milde T, Witt O, Lindroth AM, Schwartzentruber J, Faury D, Fleming A, Zakrzewska M, Liberski PP, Zakrzewski K, Hauser P, Garami M, Klekner A, Bognar L, Morrissy S, Cavalli F, Taylor MD, van Sluis P, Koster J, Versteeg R, Volckmann R, Mikkelsen T, Aldape K, Reifenberger G, Collins VP, Majewski J, Korshunov A, Lichter P, Plass C, Jabado N, Pfister SM (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22(4):425–437

    Article  CAS  PubMed  Google Scholar 

  35. Sanai N, Alvarez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353(8):811–822

    Article  CAS  PubMed  Google Scholar 

  36. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6(6):425–436

    Article  CAS  PubMed  Google Scholar 

  37. Hagg T (2009) From neurotransmitters to neurotrophic factors to neurogenesis. Neuroscientist 15(1):20–27

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Wang Y, Fan X, Zhang C, Zhang T, Peng X, Li S, Wang L, Ma J, Jiang T (2014) Anatomical specificity of O6-methylguanine DNA methyltransferase protein expression in glioblastomas. J Neurooncol 120(2):331–337

    Article  CAS  PubMed  Google Scholar 

  39. Lim DA, Cha S, Mayo MC, Chen MH, Keles E, VandenBerg S, Berger MS (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol 9(4):424–429

    Article  PubMed Central  PubMed  Google Scholar 

  40. Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S (2013) Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro Oncol 15(1):91–96

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Jha P, Suri V, Singh G, Jha P, Purkait S, Pathak P, Sharma V, Sharma MC, Suri A, Gupta D, Mahapatra AK, Sarkar C (2011) Characterization of molecular genetic alterations in GBMs highlights a distinctive molecular profile in young adults. Diagn Mol Pathol 20(4):225–232

    Article  CAS  PubMed  Google Scholar 

  42. Sawaya R, Hammoud M, Schoppa D, Hess KR, Wu SZ, Shi WM, Wildrick DM (1998) Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors. Neurosurgery 42(5):1044–1055 (discussion 1055–1046)

    Article  CAS  PubMed  Google Scholar 

  43. Yang P, Wang Y, Peng X, You G, Zhang W, Yan W, Bao Z, Wang Y, Qiu X, Jiang T (2013) Management and survival rates in patients with glioma in China (2004–2010): a retrospective study from a single-institution. J Neurooncol 113(2):259–266

    Article  CAS  PubMed  Google Scholar 

  44. Forst DA, Nahed BV, Loeffler JS, Batchelor TT (2014) Low-grade gliomas. Oncologist 19(4):403–413

    Article  PubMed Central  PubMed  Google Scholar 

  45. Chang EF, Clark A, Jensen RL, Bernstein M, Guha A, Carrabba G, Mukhopadhyay D, Kim W, Liau LM, Chang SM, Smith JS, Berger MS, McDermott MW (2009) Multiinstitutional validation of the University of California at San Francisco Low-Grade Glioma Prognostic Scoring System. Clinical article. J Neurosurg 111(2):203–210

    Article  PubMed  Google Scholar 

  46. Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, Tihan T, Vandenberg S, McDermott MW, Berger MS (2008) Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 26(8):1338–1345

    Article  PubMed  Google Scholar 

  47. Goze C, Rigau V, Gibert L, Maudelonde T, Duffau H (2009) Lack of complete 1p19q deletion in a consecutive series of 12 WHO grade II gliomas involving the insula: a marker of worse prognosis? J Neurooncol 91(1):1–5

    Article  CAS  PubMed  Google Scholar 

  48. Metellus P, Coulibaly B, Colin C, de Paula AM, Vasiljevic A, Taieb D, Barlier A, Boisselier B, Mokhtari K, Wang XW, Loundou A, Chapon F, Pineau S, Ouafik L, Chinot O, Figarella-Branger D (2010) Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis. Acta Neuropathol 120(6):719–729

    Article  PubMed  Google Scholar 

  49. Harpold HL, Alvord EC Jr, Swanson KR (2007) The evolution of mathematical modeling of glioma proliferation and invasion. J Neuropathol Exp Neurol 66(1):1–9

    Article  PubMed  Google Scholar 

  50. Swanson KR, Bridge C, Murray JD, Alvord EC Jr (2003) Virtual and real brain tumors: using mathematical modeling to quantify glioma growth and invasion. J Neurol Sci 216(1):1–10

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Yuling Yang for tissue sample collection and clinical data retrieval. This work was supported by funding from the National 973 Program (No. 2015CB755500), the National 973 Program (No. 2011CB707804), and the Research Special Fund for Public Welfare industry of health (No. 201402008).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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    Authors and Affiliations

    1. Beijing Neurosurgical Institute, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, Beijing, 100050, China

      Yinyan Wang & Tao Jiang

    2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

      Yinyan Wang, Xing Fan, Lei Wang & Tao Jiang

    3. Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

      Shuai Liu, Renzhi Wang & Wenbin Ma

    4. Department of Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

      Shaowu Li & Jun Ma

    5. China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China

      Lei Wang

    6. Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, 100069, China

      Tao Jiang

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    1. Yinyan Wang
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    Correspondence to Jun Ma, Tao Jiang or Wenbin Ma.

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    Yinyan Wang and Shuai Liu have contributed equally to this study.

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    Wang, Y., Liu, S., Fan, X. et al. Age-associated brain regions in gliomas: a volumetric analysis. J Neurooncol 123, 299–306 (2015). https://doi.org/10.1007/s11060-015-1798-x

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