Skip to main content
SpringerLink
Log in

Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Introduction

IDH1 mutation has been identified as an early genetic event driving low grade gliomas (LGGs) and it has been proven to exerts a powerful epigenetic effect. Cells containing IDH1 mutation are refractory to epigenetical reprogramming to iPSC induced by expression of Yamanaka transcription factors, a feature that we employed to study early genetic amplifications or deletions in gliomagenesis.

Methods

We made iPSC clones from freshly surgically resected IDH1 mutant LGGs by forced expression of Yamanaka transcription factors. We sequenced the IDH locus and analyzed the genetic composition of multiple iPSC clones by array-based comparative genomic hybridization (aCGH).

Results

We hypothesize that the primary cell pool isolated from LGG tumor contains a heterogeneous population consisting tumor cells at various stages of tumor progression including cells with early genetic lesions if any prior to acquisition of IDH1 mutation. Because cells containing IDH1 mutation are refractory to reprogramming, we predict that iPSC clones should originate only from LGG cells without IDH1 mutation, i.e. cells prior to acquisition of IDH1 mutation. As expected, we found that none of the iPSC clones contains IDH1 mutation. Further analysis by aCGH of the iPSC clones reveals that they contain regional chromosomal amplifications which are also present in the primary LGG cells.

Conclusions

These results indicate that there exists a subpopulation of cells harboring gene amplification but without IDH1 mutation in the LGG primary cell pool. Further analysis of TCGA LGG database demonstrates that these regional chromosomal amplifications are also present in some cases of low grade gliomas indicating they are reoccurring lesions in glioma albeit at a low frequency. Taken together, these data suggest that regional chromosomal alterations may exist prior to the acquisition of IDH mutations in at least some cases of LGGs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncology 16(Suppl 4):iv1–i63

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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 1,010 diffuse gliomas. Acta Neuropathol 118:469–474

    Article  PubMed  Google Scholar 

  4. Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O’Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, von Deimling A, Zhang H, Crain D, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG, Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD, Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S, Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J, Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV, Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J, Thiessen N, Triche T, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ, Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA, Arachchi H, Benz C, Bernard B, Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P, Ling S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R, Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D, Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T, Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ, Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K, DiMeco F, Duell R, Elder JB, Fehrenbach A, Finocchiaro G, Friedman W, Fulop J, Gardner J, Hermes B, Herold-Mende C, Jungk C, Kendler A, Lehman NL, Lipp E, Liu O, Mandt R, McGraw M, McLendon R, McPherson C, Neder L, Nguyen P, Noss A, Nunziata R, Ostrom QT, Palmer C, Perin A, Pollo B, Potapov A, Potapova O, Rathmell WK, Rotin D, Scarpace L, Schilero C, Senecal K, Shimmel K, Shurkhay V, Sifri S, Singh R, Sloan AE, Smolenski K, Staugaitis SM, Steele R, Thorne L, Tirapelli DP, Unterberg A, Vallurupalli M, Wang Y, Warnick R, Williams F, Wolinsky Y, Bell S, Rosenberg M, Stewart C, Huang F, Grimsby JL, Radenbaugh AJ, Zhang J, N Cancer Genome Atlas Research (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498

    Google Scholar 

  5. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Heiden MGV, Su SM (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pietrak B, Zhao H, Qi H, Quinn C, Gao E, Boyer JG, Concha N, Brown K, Duraiswami C, Wooster R, Sweitzer S, Schwartz B (2011) A tale of two subunits: how the neomorphic R132H IDH1 mutation enhances production of alphaHG. Biochemistry 50:4804–4812

    Article  CAS  PubMed  Google Scholar 

  7. Waitkus MS, Diplas BH, Yan H (2016) Isocitrate dehydrogenase mutations in gliomas. Neuro Oncology 18:16–26

    Article  CAS  PubMed  Google Scholar 

  8. Greaves M, Maley CC (2012) Clonal evolution in cancer. Nature 481:306–313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K, N Cancer Genome Atlas Research (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suva ML, Regev A, Bernstein BE (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344:1396–1401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA Jr, Friedman AH, Friedman H, Gallia GL, Giovanella BC, Grollman AP, He TC, He Y, Hruban RH, Jallo GI, Mandahl N, Meeker AK, Mertens F, Netto GJ, Rasheed BA, Riggins GJ, Rosenquist TA, Schiffman M, Shih Ie M, Theodorescu D, Torbenson MS, Velculescu VE, Wang TL, Wentzensen N, Wood LD, Zhang M, McLendon RE, Bigner DD, Kinzler KW, Vogelstein B, Papadopoulos N, Yan H (2013) TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA 110:6021–6026

    Article  CAS  PubMed  Google Scholar 

  12. Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G (2014) Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Venteicher AS, Tirosh I, Hebert C, Yizhak K, Neftel C, Filbin MG, Hovestadt V, Escalante LE, Shaw ML, Rodman C, Gillespie SM, Dionne D, Luo CC, Ravichandran H, Mylvaganam R, Mount C, Onozato ML, Nahed BV, Wakimoto H, Curry WT, Iafrate AJ, Rivera MN, Frosch MP, Golub TR, Brastianos PK, Getz G, Patel AP, Monje M, Cahill DP, Rozenblatt-Rosen O, Louis DN, Bernstein BE, Regev A, Suva ML (2017). Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-sEq. Science 355:eaai8478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu Z, Zhang C, Khodadadi-Jamayran A, Dang L, Han X, Kim K, Li H, Zhao R (2017) Canonical microRNAs enable differentiation, protect against dna damage, and promote cholesterol biosynthesis in neural stem cells. Stem Cells Dev 26:177–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Han X, Zhang W, Yang X, Wheeler CG, Langford CP, Wu L, Filippova N, Friedman GK, Ding Q, Fathallah-Shaykh HM, Gillespie GY, Nabors LB (2014) The role of Src family kinases in growth and migration of glioma stem cells. Int J Oncol 45:302–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rana U, Liu Z, Kumar SN, Zhao B, Hu W, Bordas M, Cossette S, Szabo S, Foeckler J, Weiler H, Chrzanowska-Wodnicka M, Holtz ML, Misra RP, Salato V, North PE, Ramchandran R, Miao QR (2016) Nogo-B receptor deficiency causes cerebral vasculature defects during embryonic development in mice. Dev Biol 410:190–201

    Article  CAS  PubMed  Google Scholar 

  18. Somers A, Jean JC, Sommer CA, Omari A, Ford CC, Mills JA, Ying L, Sommer AG, Jean JM, Smith BW, Lafyatis R, Demierre MF, Weiss DJ, French DL, Gadue P, Murphy GJ, Mostoslavsky G, Kotton DN (2010) Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette. Stem Cells 28:1728–1740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhao R, Deibler RW, Lerou PH, Ballabeni A, Heffner GC, Cahan P, Unternaehrer JJ, Kirschner MW, Daley GQ (2014) A nontranscriptional role for Oct4 in the regulation of mitotic entry. Proc Natl Acad Sci USA 111:15768–15773

    Article  CAS  PubMed  Google Scholar 

  20. Liu Z, Zhao R (2016) Generation of HEXA-deficient hiPSCs from fibroblasts of a Tay-Sachs disease patient. Stem Cell Res 17:289–291

    Article  CAS  PubMed  Google Scholar 

  21. Beers J, Gulbranson DR, George N, Siniscalchi LI, Jones J, Thomson JA, Chen G (2012) Passaging and colony expansion of human pluripotent stem cells by enzyme-free dissociation in chemically defined culture conditions. Nat Protoc 7:2029–2040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Park IH, Lerou PH, Zhao R, Huo H, Daley GQ (2008) Generation of human-induced pluripotent stem cells. Nat Protoc 3:1180–1186

    Article  CAS  PubMed  Google Scholar 

  23. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146

    Article  CAS  PubMed  Google Scholar 

  24. Kim K, Zhao R, Doi A, Ng K, Unternaehrer J, Cahan P, Huo H, Loh YH, Aryee MJ, Lensch MW, Li H, Collins JJ, Feinberg AP, Daley GQ (2011) Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol 29:1117–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu Z, Skamagki M, Kim K, Zhao R (2015) Canonical microRNA activity facilitates but may be dispensable for transcription factor-mediated reprogramming. Stem Cell Rep 5:1119–1127

    Article  CAS  Google Scholar 

  26. Woolnough JL, Atwood BL, Liu Z, Zhao R, Giles KE (2016) The regulation of rRNA gene transcription during directed differentiation of human embryonic stem cells. PLoS ONE 11:e0157276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liu Z, Zhang C, Skamagki M, Khodadadi-Jamayran A, Zhang W, Kong D, Chang CW, Feng J, Han X, Townes TM, Li H, Kim K, Zhao R (2017) Elevated p53 activities restrict differentiation potential of microrna-deficient pluripotent stem cells. Stem Cell Rep 9:1604–1617

    Article  CAS  Google Scholar 

  28. MacDonald JR, Ziman R, Yuen RK, Feuk L, Scherer SW (2014) The database of genomic variants: a curated collection of structural variation in the human genome. Nucleic Acids Res 42:D986–D992

    Article  CAS  PubMed  Google Scholar 

  29. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Sig 6:pl1

    Google Scholar 

  30. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404

    Article  Google Scholar 

  31. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  Google Scholar 

  32. Luchman HA, Stechishin OD, Dang NH, Blough MD, Chesnelong C, Kelly JJ, Nguyen SA, Chan JA, Weljie AM, Cairncross JG, Weiss S (2012) An in vivo patient-derived model of endogenous IDH1-mutant glioma. NeuroOncology 14:184–191

    CAS  Google Scholar 

  33. Gopalakrishnan V (2009) REST and the RESTless: in stem cells and beyond. Future Neurol 4:317–329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lunyak VV, Rosenfeld MG (2005) No rest for REST: REST/NRSF regulation of neurogenesis. Cell 121:499–501

    Article  CAS  PubMed  Google Scholar 

  35. Kamal MM, Sathyan P, Singh SK, Zinn PO, Marisetty AL, Liang S, Gumin J, El-Mesallamy HO, Suki D, Colman H, Fuller GN, Lang FF, Majumder S (2012) REST regulates oncogenic properties of glioblastoma stem cells. Stem Cells 30:405–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Conti L, Crisafulli L, Caldera V, Tortoreto M, Brilli E, Conforti P, Zunino F, Magrassi L, Schiffer D, Cattaneo E (2012) REST controls self-renewal and tumorigenic competence of human glioblastoma cells. PLoS ONE 7:e38486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liang J, Meng Q, Zhao W, Tong P, Li P, Zhao Y, Zhao X, Li H (2016) An expression based REST signature predicts patient survival and therapeutic response for glioblastoma multiforme. Sci Rep 6:34556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Choi J, Lee S, Mallard W, Clement K, Tagliazucchi GM, Lim H, Choi IY, Ferrari F, Tsankov AM, Pop R, Lee G, Rinn JL, Meissner A, Park PJ, Hochedlinger K (2015) A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs. Nat Biotechnol 33:1173–1181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cohen A, Sato M, Aldape K, Mason CC, Alfaro-Munoz K, Heathcock L, South ST, Abegglen LM, Schiffman JD, Colman H (2015) DNA copy number analysis of Grade II-III and Grade IV gliomas reveals differences in molecular ontogeny including chromothripsis associated with IDH mutation status. Acta Neuropathol Commun 3:34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kotini AG, Chang CJ, Chow A, Yuan H, Ho TC, Wang T, Vora S, Solovyov A, Husser C, Olszewska M, Teruya-Feldstein J, Perumal D, Klimek VM, Spyridonidis A, Rampal RK, Silverman L, Reddy EP, Papaemmanuil E, Parekh S, Greenbaum BD, Leslie CS, Kharas MG, Papapetrou EP (2017) Stage-specific human induced pluripotent stem cells map the progression of myeloid transformation to transplantable leukemia. Cell Stem Cell 20:315–328 e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhao R, Daley GQ (2008) From fibroblasts to iPS cells: induced pluripotency by defined factors. J Cell Biochem 105:949–955

    Article  CAS  PubMed  Google Scholar 

  42. Ichimura K, Pearson DM, Kocialkowski S, Backlund LM, Chan R, Jones DT, Collins VP (2009) IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncology 11:341–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jin G, Reitman ZJ, Duncan CG, Spasojevic I, Gooden DM, Rasheed BA, Yang R, Lopez GY, He Y, McLendon RE, Bigner DD, Yan H (2013) Disruption of wild-type IDH1 suppresses D-2-hydroxyglutarate production in IDH1-mutated gliomas. Cancer Res 73:496–501

    Article  CAS  PubMed  Google Scholar 

  44. Yu M, Yu S, Xue Y, Yu H, Chen D, Wei X, Liu Y (2018) Over-expressed FEZF1 predicts a poor prognosis in glioma and promotes glioma cell malignant biological properties by regulating Akt-ERK pathway. J Mol Neurosci 65:411–419

    Article  CAS  PubMed  Google Scholar 

  45. Azar S, Leventoux N, Ripoll C, Rigau V, Goze C, Lorcy F, Bauchet L, Duffau H, Guichet PO, Rothhut B, Hugnot JP (2018) Cellular and molecular characterization of IDH1-mutated diffuse low grade gliomas reveals tumor heterogeneity and absence of EGFR/PDGFRalpha activation. Glia 66:239–255

    Article  CAS  PubMed  Google Scholar 

  46. Bao ZS, Chen HM, Yang MY, Zhang CB, Yu K, Ye WL, Hu BQ, Yan W, Zhang W, Akers J, Ramakrishnan V, Li J, Carter B, Liu YW, Hu HM, Wang Z, Li MY, Yao K, Qiu XG, Kang CS, You YP, Fan XL, Song WS, Li RQ, Su XD, Chen CC, Jiang T (2014) RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas. Genome Res 24:1765–1773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li Y, Wang D, Wang L, Yu J, Du D, Chen Y, Gao P, Wang DM, Yu J, Zhang F, Fu S (2013) Distinct genomic aberrations between low-grade and high-grade gliomas of Chinese patients. PLoS ONE 8:e57168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rice T, Zheng S, Decker PA, Walsh KM, Bracci P, Xiao Y, McCoy LS, Smirnov I, Patoka JS, Hansen HM, Hsuang G, Wiemels JL, Tihan T, Pico AR, Prados MD, Chang SM, Berger MS, Caron A, Fink S, Kollmeyer T, Rynearson A, Voss J, Kosel ML, Fridley BL, Lachance DH, Eckel-Passow JE, Sicotte H, O’Neill BP, Giannini C, Wiencke JK, Jenkins RB, Wrensch MR (2013) Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology. Neuro Oncology 15:535–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jenkins RB, Xiao Y, Sicotte H, Decker PA, Kollmeyer TM, Hansen HM, Kosel ML, Zheng S, Walsh KM, Rice T, Bracci P, McCoy LS, Smirnov I, Patoka JS, Hsuang G, Wiemels JL, Tihan T, Pico AR, Prados MD, Chang SM, Berger MS, Caron AA, Fink SR, Halder C, Rynearson AL, Fridley BL, Buckner JC, O’Neill BP, Giannini C, Lachance DH, Wiencke JK, Eckel-Passow JE, Wrensch MR (2012) A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. Nat Genet 44:1122–1125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ozawa T, Riester M, Cheng YK, Huse JT, Squatrito M, Helmy K, Charles N, Michor F, Holland EC (2014) Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma. Cancer Cell 26:288–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This project is supported by the UAB CCC Neuro-oncology Research Acceleration Fund. X.H. and R.Z. are supported by the NIH grant R21NS106430. X.H. is supported by the NIH grant 1R01NS095626. R.Z. is supported by is supported by Institutional Research Grant number 128599-IRG-15-56-IRG from the American Cancer Society, Faculty Development Grant Program award, and UAB CFRC Pilot & Feasibility Grant (ROWE15R0). K.K. is supported by NIH (5R00HL093212-04), TriStem-Star Foundation (2013-049), Louis V. Gerstner, Jr. Young Investigators awards, Geoffrey Beene Junior Chair Award, Sidney Kimmel Scholar Award, Alfred W. Bressler Scholars Endowment Fund, and MSKCC Society Fund. This study was funded by National Heart, Lung, and Blood Institute (US) (Grant No. HL085324) and National Heart, Lung, and Blood Institute (Grant No. HL127338).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Zhong Liu, Xinyang Zhao & Rui Zhao

  2. Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Pulin Che, Burt Nabors & Xiaosi Han

  3. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Juan J. Mercado & James R. Hackney

  4. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    James R. Hackney, Gregory K. Friedman & James M. Markert

  5. Department of Molecular Pharmacology & Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55904, USA

    Cheng Zhang & Hu Li

  6. Department of Medicine, University of Colorado Denver-Anschutz Medical Campus, Denver, CO, 80045, USA

    Zhiying You

  7. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Qiang Ding

  8. Cancer Biology and Genetics Program, The Center for Cell Engineering, The Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute for Cancer Research, New York, NY, USA

    Kitai Kim

  9. Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY, 10065, USA

    Kitai Kim

  10. Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Xiaoguang Liu

  11. Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    James M. Markert & G. Yancey Gillespie

  12. University of Alabama at Birmingham, Shelby 714, 1825 University Blvd., Birmingham, AL, 35294, USA

    Rui Zhao

  13. University of Alabama at Birmingham, 1020 Faculty Office Tower, 510 20th Street South, Birmingham, AL, 35294, USA

    Xiaosi Han

Authors
  1. Zhong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pulin Che
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juan J. Mercado
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James R. Hackney
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gregory K. Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhiying You
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xinyang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Qiang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kitai Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xiaoguang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. James M. Markert
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Burt Nabors
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. G. Yancey Gillespie
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Rui Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Xiaosi Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Rui Zhao or Xiaosi Han.

Ethics declarations

Conflict of interest

The authors indicate no potential conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 124 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Z., Che, P., Mercado, J.J. et al. Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis. J Neurooncol 141, 289–301 (2019). https://doi.org/10.1007/s11060-018-03047-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-018-03047-1

Keywords

Search

Navigation