Molecular Heterogeneity of Glioblastoma and its Clinical Relevance

Pathology and Oncology Research

Volumn 20, Issue 4, 2014, Pages 777-787

  Eder, Katalin ^a   Kalman, Bernadette ^a,b  

^a Markusovszky University Teaching Hospital   (Hungary)

^b UNIVERSITY OF PÉCS   (Hungary)

Author keywords

Glioblastoma; Inter tumor heterogeneity; Intra tumor heterogeneity; Molecular classification; Molecular heterogeneity; Primary brain tumor

Indexed keywords

CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE INHIBITOR 2A; EPIDERMAL GROWTH FACTOR RECEPTOR; ISOCITRATE DEHYDROGENASE 1; MICRORNA; NEUROFIBROMIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P53; PROTEIN TYROSINE KINASE; RETINOBLASTOMA BINDING PROTEIN;

CANCER CLASSIFICATION; CANCER DIAGNOSIS; CANCER RESEARCH; CANCER RISK; CANCER STEM CELL; CANCER THERAPY; CHROMOSOME; COMPARATIVE GENOMIC HYBRIDIZATION; COPY NUMBER VARIATION; CPG ISLAND; DNA FINGERPRINTING; DNA METHYLATION; EPIGENETICS; FLOW CYTOMETRY; GENE DELETION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE SEQUENCE; GENETIC VARIABILITY; GENOME; GLIOBLASTOMA; HISTOPATHOLOGY; KARYOTYPING; MOLECULAR DIAGNOSTICS; MOLECULAR PATHOLOGY; PERSONALIZED MEDICINE; PHENOTYPE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SOMATIC MUTATION; TRANSCRIPTOMICS; TUMOR MOLECULAR HETEROGENEITY; CLASSIFICATION; GENETICS; HUMAN; PATHOLOGY; PROGNOSIS;

GENETIC VARIATION; GLIOBLASTOMA; HUMANS; PROGNOSIS;

EID: 84919882983     PISSN: 12194956     EISSN: 15322807     Source Type: Journal    
DOI: 10.1007/s12253-014-9833-3     Document Type: Review

References (53)

1. Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-Oncol 14(suppl 5):v1–v49
2. Olar A, Aldape KD (2014) Using the molecular classification of glioblastoma to inform personalized treatment. J Pathol 232(2):165–177
3. Burger PC, Green SB (1987) Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59(9):1617–1625
4. Shapiro JR, Yung WK, Shapiro WR (1981) Isolation, karyotype, and clonal growth of heterogeneous subpopulations of human malignant gliomas. Cancer Res 41(6):2349–2359
5. Loeper S, Romeike B, Heckmann N, Jung V, Henn W, Feiden W, Zang K, Urbschat S (2001) Frequent mitotic errors in tumor cells of genetically micro-heterogeneous glioblastomas. Cytogenet Genome Res 94(1–2):1–8
6. Coons SW, Johnson PC, Shapiro JR (1995) Cytogenetic and flow cytometry DNA analysis of regional heterogeneity in a low grade human glioma. Cancer Res 55(7):1569–1577
7. Misra A, Chattopadhyay P, Dinda AK, Sarkar C, Mahapatra AK, Hasnain SE, Sinha S (2000) Extensive intra-tumor heterogeneity in primary human glial tumors as a result of locus non-specific genomic alterations. J Neuro-Oncol 48(1):1–12
8. Harada K, Nishizaki T, Ozaki S, Kubota H, Ito H, Sasaki K (1998) Intratumoral cytogenetic heterogeneity detected by comparative genomic hybridization and laser scanning cytometry in human gliomas. Cancer Res 58(20):4694–4700
9. Walker C, du Plessis DG, Joyce KA, Machell Y, Thomson-Hehir J, Al Haddad SA, Broome JC, Warnke PC (2003) Phenotype versus genotype in gliomas displaying inter-or intratumoral histological heterogeneity. Clin Cancer Res 9(13):4841–4851
10. Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21(21):2683–2710
11. McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis GM, Olson JJ, Mikkelsen T, Lehman N, Aldape K (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nat 455(7216):1061–1068
12. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Sci 321(5897):1807–1812. doi:10.1126/science.1164382
13. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1):98–110. doi:10.1016/j.ccr.2009.12.020
14. Masica DL, Karchin R (2011) Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival. Cancer Res 71(13):4550–4561
15. Cerami E, Demir E, Schultz N, Taylor BS, Sander C (2010) Automated network analysis identifies core pathways in glioblastoma. PLoS One 5(2):e8918
16. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C (2007) Patterns of somatic mutation in human cancer genomes. Nat 446(7132):153–158
17. Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nat 458(7239):719–724
18. Ahn J-Y, Hu Y, Kroll TG, Allard P, Ye K (2004) PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt. Proc Natl Acad Sci U S A 101(18):6993–6998
19. Qi Q, He K, Liu X, Pham C, Meyerkord C, Fu H, Ye K (2013) Disrupting the PIKE-A/Akt interaction inhibits glioblastoma cell survival, migration, invasion and colony formation. Oncog 32(8):1030–1040
20. Frattini V, Trifonov V, Chan JM, Castano A, Lia M, Abate F, Keir ST, Ji AX, Zoppoli P, Niola F (2013) The integrated landscape of driver genomic alterations in glioblastoma. Nat Genet 45(10):1141–1149
21. Pugh TJ, Weeraratne SD, Archer TC, Krummel DAP, Auclair D, Bochicchio J, Carneiro MO, Carter SL, Cibulskis K, Erlich RL (2012) Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nat 488(7409):106–110
22. Zhang J, Benavente CA, McEvoy J, Flores-Otero J, Ding L, Chen X, Ulyanov A, Wu G, Wilson M, Wang J (2012) A novel retinoblastoma therapy from genomic and epigenetic analyses. Nat 481(7381):329–334
23. Network CGAR (2013) Integrated genomic characterization of endometrial carcinoma. Nat 497(7447):67–73
24. Freije WA, Castro-Vargas FE, Fang Z, Horvath S, Cloughesy T, Liau LM, Mischel PS, Nelson SF (2004) Gene expression profiling of gliomas strongly predicts survival. Cancer Res 64(18):6503–6510
25. Liang Y, Diehn M, Watson N, Bollen AW, Aldape KD, Nicholas MK, Lamborn KR, Berger MS, Botstein D, Brown PO (2005) Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci U S A 102(16):5814–5819
26. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9(3):157–173
27. Kong J, Cooper LA, Wang F, Gutman DA, Gao J, Chisolm C, Sharma A, Pan T, Van Meir EG, Kurc TM (2011) Integrative, multimodal analysis of glioblastoma using TCGA molecular data, pathology images, and clinical outcomes. Biomed Eng, IEEE Trans on 58(12):3469–3474
28. Kim Y-W, Koul D, Kim SH, Lucio-Eterovic AK, Freire PR, Yao J, Wang J, Almeida JS, Aldape K, Yung WA (2013) Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis. Neuro-Oncol 15(7):829–839
29. Doucette T, Rao G, Rao A, Shen L, Aldape K, Wei J, Dziurzynski K, Gilbert M, Heimberger AB (2013) Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas. Cancer Immunol Res 1(2):112–122
30. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128(4):683–692
31. 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 (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17(5):510–522. doi:10.1016/j.ccr.2010.03.017
32. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH (2013) The somatic genomic landscape of glioblastoma. Cell 155(2):462–477
33. Li B, Senbabaoglu Y, Peng W, Yang M-L, Xu J, Li JZ (2012) Genomic estimates of aneuploid content in glioblastoma multiforme and improved classification. Clin Cancer Res 18(20):5595–5605
34. Iorio MV, Croce CM (2012) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4(3):143–159
35. Kim T-M, Huang W, Park R, Park PJ, Johnson MD (2011) A developmental taxonomy of glioblastoma defined and maintained by MicroRNAs. Cancer Res 71(9):3387–3399
36. Li R, Gao K, Luo H, Wang X, Shi Y, Dong Q, Luan W, You Y (2014) Identification of intrinsic subtype-specific prognostic microRNAs in primary glioblastoma. J Exp Clin Cancer Res 33(1):9
37. Godlewski J, Newton H, Chiocca E, Lawler S (2010) MicroRNAs and glioblastoma; the stem cell connection. Cell Death Differ 17(2):221–228
38. Hermansen SK, Kristensen BW (2013) MicroRNA biomarkers in glioblastoma. J Neuro-Oncol 114(1):13–23
39. Dirks PB (2010) Brain tumor stem cells: the cancer stem cell hypothesis writ large. Mol Oncol 4(5):420–430
40. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nat 432(7015):396–401
41. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64(19):7011–7021
42. Lottaz C, Beier D, Meyer K, Kumar P, Hermann A, Schwarz J, Junker M, Oefner PJ, Bogdahn U, Wischhusen J (2010) Transcriptional profiles of CD133+ and CD133− glioblastoma-derived cancer stem cell lines suggest different cells of origin. Cancer Res 70(5):2030–2040
43. De Bacco F, Casanova E, Medico E, Pellegatta S, Orzan F, Albano R, Luraghi P, Reato G, D’Ambrosio A, Porrati P (2012) The MET oncogene is a functional marker of a glioblastoma stem cell subtype. Cancer Res 72(17):4537–4550
44. Weller M, Stupp R, Hegi ME, van den Bent M, Tonn JC, Sanson M, Wick W, Reifenberger G (2012) Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice. Neuro-Oncol 14(suppl 4):iv100–iv108
45. Marko NF, Quackenbush J, Weil RJ (2011) Why is there a lack of consensus on molecular subgroups of glioblastoma? Understanding the nature of biological and statistical variability in glioblastoma expression data. PLoS One 6(7):e20826
46. Nobusawa S, Lachuer J, Wierinckx A, Kim YH, Huang J, Legras C, Kleihues P, Ohgaki H (2010) Intratumoral patterns of genomic imbalance in glioblastomas. Brain Pathol 20(5):936–944. doi:10.1111/j.1750-3639.2010.00395.x
47. Snuderl M, Fazlollahi L, Le LP, Nitta M, Zhelyazkova BH, Davidson CJ, Akhavanfard S, Cahill DP, Aldape KD, Betensky RA (2011) Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell 20(6):810–817
48. Little SE, Popov S, Jury A, Bax DA, Doey L, Al-Sarraj S, Jurgensmeier JM, Jones C (2012) Receptor tyrosine kinase genes amplified in glioblastoma exhibit a mutual exclusivity in variable proportions reflective of individual tumor heterogeneity. Cancer Res 72(7):1614–1620
49. Szerlip NJ, Pedraza A, Chakravarty D, Azim M, McGuire J, Fang Y, Ozawa T, Holland EC, Huse JT, Jhanwar S (2012) Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci 109(8):3041–3046
50. Sottoriva A, Spiteri I, Piccirillo SG, Touloumis A, Collins VP, Marioni JC, Curtis C, Watts C, Tavare S (2013) Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A 110(10):4009–4014. doi:10.1073/pnas.1219747110
51. Purow B, Schiff D (2009) Advances in the genetics of glioblastoma: are we reaching critical mass? Nat Rev Neurol 5(8):419–426
52. Ikediobi O (2008) Somatic pharmacogenomics in cancer. Pharmacogenomics J 8(5):305–314
53. Inda M-d-M, Bonavia R, Seoane J (2014) Glioblastoma multiforme: a look inside its heterogeneous nature. Cancers 6(1):226–239