Studying a complex tumor: Potential and pitfalls

Cancer Journal

Volumn 18, Issue 1, 2012, Pages 107-114

  Zheng, Siyuan ^a   Chheda, Milan G ^b   Verhaak, Roel G W ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

expression profiling; genomics; Glioblastoma; molecular subtypes; personalized medicine; sequencing

Indexed keywords

PROTEIN P53; VASCULOTROPIN;

CLINICAL TRIAL (TOPIC); GENE DOSAGE; GENE EXPRESSION PROFILING; GENETICS; GENOME ANALYSIS; GLIOBLASTOMA; HUMAN; ONCOGENE; PATHOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROGNOSIS; REVIEW; TUMOR SUPPRESSOR GENE;

BRAIN NEOPLASMS; GENE EXPRESSION PROFILING; GENE THERAPY; GENOMICS; GLIOBLASTOMA; HUMANS;

EID: 84856722847     PISSN: 15289117     EISSN: 1540336X     Source Type: Journal    
DOI: 10.1097/PPO.0b013e3182431c57     Document Type: Review

References (100)

1. Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol. 2005;109:93-108. (Pubitemid 40287792)
2. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005; 1352:997-1003. (Pubitemid 40349502)
3. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epi-dermal growth factorreceptorunderlying responsiveness ofnon-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129-2139. (Pubitemid 38637993)
4. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304:1497-1500. (Pubitemid 38720929)
5. Rich JN, Hans C, Jones B, et al. Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res. 2005;65:4051-4058. (Pubitemid 40775641)
6. Liang Y, Diehn M, Watson N, et al. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multi-forme. Proc Natl Acad Sci US A. 2005;102:5814-5819. (Pubitemid 40559642)
7. Hui AB, Lo KW, Yin XL, et al. Detection ofmultiple gene amplific-ations in glioblastoma multiforme using array-based comparative ge-nomic hybridization. Lab Invest. 2001;81:717-723. (Pubitemid 32466534)
8. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807-1812.
9. Murat A, Migliavacca E, Gorlia T, et al. Stem cell-related ''self-renewal'' signature and high epidermal growth factor receptor expression asso-ciated with resistance to concomitant chemoradiotherapy in glioblas-toma. J Clin Oncol. 2008;26:3015-3024.
10. Beroukhim R, Getz G, Nghiemphu L, et al. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci U S A. 2007;104:20007-20012.
11. Bredel M, Scholtens DM, Yadav AK, et al. NFKBIA deletion in glio-blastomas. NEngl JMed. 2011;364:627-637.
12. Carro MS, Lim WK, Alvarez MJ, et al. The transcriptional network for-mesenchymal transformation of brain tumours. Nature. 2010;463: 318-325.
13. Li A, Walling J, Ahn S, et al. Unsupervised analysis oftranscriptomic profiles reveals six glioma subtypes. Cancer Res. 2009;69:2091-2099.
14. Mischel PS, Shai R, Shi T, et al. Identification of molecular sub-types of glioblastoma by gene expression profiling. Oncogene. 2003; 22:2361-2373. (Pubitemid 36566791)
15. Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a Cp G island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17:510-522.
16. Nutt CL, Mani DR, Betensky RA, et al. Gene expression-based clas-sification of malignant gliomas correlates better with survival than histological classification. Cancer Res. 2003;63:1602-1607. (Pubitemid 36373650)
17. Ozawa T, Brennan CW, Wang L, et al. PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. Genes Dev. 2010;24:2205-2218.
18. Phillips HS, Kharbanda S, Chen R, et al. Molecular subclasses ofhigh-grade glioma predict prognosis, delineate a pattern ofdisease progression, and resemble stages in neurogenesis. Cancer Cell. 2006;9:157-173. (Pubitemid 43357943)
19. Rothenberg SM, Mohapatra G, Rivera MN, et al. A genome-wide sc-reen for microdeletions reveals disruption ofpolarity complex genes in diverse human cancers. Cancer Res. 2010;70:2158-2164
20. TCGA. Comprehensive genomic characterization defines human glio-blastoma genes and core pathways. Nature. 2008;455:1061-1068.
21. Tso CL, Freije WA, Day A, et al. Distinct transcription profiles of primary and secondary glioblastoma subgroups. Cancer Res. 2006;66: 159-167. (Pubitemid 43166021)
22. Veeriah S, Brennan C, Meng S, et al. The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma andotherhuman cancers. Proc Natl Acad Sci USA. 2009; 106:9435-9440.
23. Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic anal-ysis identifies clinically relevant subtypes of glioblastoma character-ized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98-110.
24. Ciriello G, Cerami EG, Sander C, et al. Mutual exclusivity analysis identifies oncogenic network modules. Genome Res. [published online ahead ofprint Oct 12, 2011].
25. Bredel M, Scholtens DM, Harsh GR, et al. A network model of a cooperative genetic landscape in brain tumors. JAMA. 2009;302: 261-275.
26. Cerami E, Demir E, Schultz N, et al. Automated network analysis identifies core pathways in glioblastoma. PLo S One. 2010;5:e8918.
27. Huse JT, Holland EC Targeting brain cancer: advances in the molec-ular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 2010;10:319-331.
28. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classifica-tion oftumours of the central nervous system. Acta Neuropathol. 2007; 114:97-109. (Pubitemid 47103521)
29. van den Bent MJ. Interobserver variation of the histopathological di-agnosis in clinical trials on glioma: a clinician's perspective. Acta Neuropathol. 2010;120:297-304.
30. Coons SW, Johnson PC, Scheithauer BW, et al. Improving diagnostic accuracy and interobserver concordance in the classification and grad-ing ofprimary gliomas. Cancer. 1997;79:1381-1393. (Pubitemid 27143246)
31. Giannini C, Scheithauer BW, Weaver AL, et al. Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grad-ing. JNeuropathol Exp Neurol. 2001;60:248-262. (Pubitemid 32209644)
32. Dunn J, Baborie A, Alam F, et al. Extent of MGMT promoter methyl-ation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br JCancer. 2009;101:124-131.
33. Nobusawa S, Lachuer J, Wierinckx A, et al. Intratumoral patterns of genomic imbalance in glioblastomas. Brain Pathol. 2010;20:936-944.
34. Vital AL, Tabernero MD, Crespo I, et al. Intratumoral patterns ofclonal evolution in gliomas. Neurogenetics. 2010;11:227-239.
35. Ren ZP, Olofsson T, Qu M, et al. Molecular genetic analysis of p53 intratumoral heterogeneity in human astrocytic brain tumors. J Neuro-pathol Exp Neurol. 2007;66:944-954. (Pubitemid 47530833)
36. Bonavia R, Inda MM, Cavenee WK, et al. Heterogeneity maintenance in glioblastoma: asocialnetwork. Cancer Res. 2011;71:4055-4060.
37. Chen R, Nishimura MC, Bumbaca SM, et al. A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell. 2010;17:362-375.
38. Navin N, Kendall J, Troge J, etal. Tumourevolution inferredby single-cell sequencing. Nature. 2011;472:90-94.
39. Pao W, Miller VA, Politi KA, et al. Acquired resistance oflung adeno-carcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLo SMed. 2005;2:e73.
40. Freije WA, Castro-Vargas FE, Fang Z, et al. Gene expression profil-ing of gliomas strongly predicts survival. Cancer Res. 2004;64: 6503-6510. (Pubitemid 39297907)
41. Sun L, Hui AM, Su Q,et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell. 2006;9:287-300.
42. Wiedemeyer R, Brennan C, Heffernan TP, et al. Feedback circuit among INK4 tumor suppressors constrains human glioblastoma development. Cancer Cell. 2008;13:355-364. (Pubitemid 351454058)
43. Solomon DA, Kim JS, Jenkins S, et al. Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme. Cancer Res. 2008;68:2564-2569. (Pubitemid 351556252)
44. Duncan CG, Killela PJ, Payne CA, et al. Integrated genomic analyses identify ERRFI1 and TACC3 as glioblastoma-targeted genes. Oncotar-get.2010;1: 265-277.
45. Song SW, Fuller GN, Zheng H, et al. Inactivation of the invasion in-hibitory gene IIp45 by alternative splicing in gliomas. Cancer Res. 2005;65:3562-3567. (Pubitemid 40616331)
46. Bagchi A, Papazoglu C, Wu Y, et al. CHD5 is a tumor suppressor at human 1p36. Cell. 2007;128:459-475. (Pubitemid 46198889)
47. Ichimura K, Vogazianou AP, Liu L, et al. 1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset ofglioblastomas. Oncogene. 2008;27:2097-2108. (Pubitemid 351442746)
48. Riemenschneider MJ, Buschges R, Wolter M, et al. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res. 1999;59:6091-6096. (Pubitemid 30035626)
49. Yin D, Ogawa S, Kawamata N, et al. High-resolution genomic copy number profiling of glioblastoma multiforme by single nucleotide polymorphism DNA microarray. Mol Cancer Res. 2009;7:665-677.
50. Roversi G, Pfundt R, Moroni RF, et al. Identification ofnovel geno-mic markers related to progression to glioblastoma through geno-mic profiling of25 primary glioma cell lines. Oncogene. 2006;25: 1571-1583. (Pubitemid 43361942)
51. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. NEngl JMed. 2009;360:765-773.
52. Samuels Y, Wang Z, Bardelli A, et al. High frequency ofmutations of the PIK3CA gene in human cancers. Science. 2004;304:554. (Pubitemid 38541907)
53. Annovazzi L, Mellai M, Caldera V, et al. SOX2 expression and amplification in gliomas and glioma cell lines. Cancer Genomics. Proteomics. 2011;8:139-147.
54. Schmitz M, Temme A, Senner V, et al. Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy. Br JCancer. 2007;96:1293-1301. (Pubitemid 46625072)
55. Veeriah S,Taylor BS, Meng S,etal. Somaticmutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malig-nancies. Nat Genet. 2010;42:77-82.
56. Ekstrand AJ, Sugawa N, James CD, et al. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions ofsequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci USA. 1992;89:4309-4313.
57. Frederick L, Wang XY, Eley G, et al. Diversity and frequency ofepi-dermal growth factor receptor mutations in human glioblastomas. Cancer Res. 2000;60:1383-1387. (Pubitemid 30152011)
58. Wiedemeyer WR, Dunn IF, Quayle SN, et al. Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM. Proc Natl Acad Sci U S A. 2010;107:11501-11506.
59. Fischer U, Muller HW, Sattler HP, et al. Amplification of the MET gene in glioma. Genes Chromosomes Cancer. 1995;12:63-65.
60. Basto D, Trovisco V, Lopes JM, et al. Mutation analysis of B-RAFgene in human gliomas. Acta Neuropathol. 2005;109:207-210. (Pubitemid 40468390)
61. Schmidt EE, Ichimura K, Reifenberger G, et al. CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glio-blastomas. Cancer Res. 1994;54:6321-6324.
62. Wang SI, Puc J, Li J, et al. Somatic mutations of PTENin glioblastoma multiforme. Cancer Res. 1997;57:4183-4186. (Pubitemid 27413419)
63. Rollbrocker B, Waha A, Louis DN, et al. Amplification of the cyclin-dependent kinase 4 (CDK4) gene is associated with high cdk4 protein levels in glioblastoma multiforme. Acta Neuropathol. 1996;92:70-74. (Pubitemid 26192085)
64. Biernat W, Kleihues P, Yonekawa Y, et al. Amplification and over-expression of MDM2 in primary (de novo) glioblastomas. J Neuro-pathol Exp Neurol. 1997;56:180-185. (Pubitemid 27461181)
65. INK4A, MTS1) and CDK4 genes have frequent mutations of the retinoblastoma gene. Oncogene. 1996; 13:1065-1072. (Pubitemid 26329093)
66. Chung R, Whaley J, Kley N, et al. TP53 gene mutations and 17p de-letions in human astrocytomas. Genes Chromosomes Cancer. 1991;3: 323-331.
67. Stegh AH, Brennan C,Mahoney JA,etal. Gliomaoncoprotein Bcl2L12 inhibits the p53 tumor suppressor. Genes Dev. 2010;24:2194-2204.
68. Tchirkov A, Rolhion C, Bertrand S, et al. IL-6 gene amplification and expression in human glioblastomas. Br J Cancer. 2001;85:518-522. (Pubitemid 32808274)
69. Van Meir E, Sawamura Y, Diserens AC, et al. Human glioblastoma cells release interleukin 6 in vivo and in vitro. Cancer Res. 1990;50: 6683-6688. (Pubitemid 20348800)
70. Buschges R, Weber RG, Actor B, et al. Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas. Brain Pathol. 1999;9:435-442; discussion 32-33.
71. Bigner SH, Mark J, Burger PC, et al. Specific chromosomal abnormali-ties in malignant human gliomas. Cancer Res. 1988;48:405-411. (Pubitemid 18045778)
72. Wrensch M, Jenkins RB, Chang JS, et al. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009;41:905-908.
73. Shete S, Hosking FJ, Robertson LB, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009;41: 899-904.
74. Clark MJ, Homer N, O'Connor BD, et al. U87MG decoded: the geno-mic sequence of a cytogenetically aberrant human cancer cell line. PLo SGenet. 2010;6:e1000832.
75. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, et al. PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron. 2006; 51:187-199. (Pubitemid 44063617)
76. Liu C, Sage JC, Miller MR, et al. Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. 2011;146:209-221.
77. Kaufmann K, Bach K, Thiel G. The extracellular signal-regulated pro-tein kinases Erk1/Erk2 stimulate expression and biological activity of the transcriptional regulator Egr-1. Biol Chem. 2001;382:1077-1081. (Pubitemid 32750605)
78. Jornsten R, Abenius T, Kling T, et al. Network modeling of the tran-scriptional effects ofcopy number aberrations in glioblastoma. Mol Syst Biol. 2011;7:486.
79. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leuke-mia. NEngl JMed. 2001;344:1031-1037. (Pubitemid 32267972)
80. Stommel JM, Kimmelman AC, Ying H, et al. Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted thera-pies. Science. 2007;318:287-290. (Pubitemid 47574858)
81. De Witt Hamer PC Small molecule kinase inhibitors in glioblas-toma: a systematic review ofclinical studies. Neuro Oncol. 2010;12:304-316.
82. Raizer JJ, Abrey LE, Lassman AB, et al. A phase II trial oferlotinib in patients with recurrent malignant gliomas and nonprogressive glio-blastoma multiforme postradiation therapy. Neuro Oncol. 2010;12: 95-103.
83. Belda-Iniesta C, Carpeno Jde C, Saenz EC, et al. Long term responses with cetuximab therapy in glioblastoma multiforme. Cancer Biol Ther. 2006;5:912-914.
84. Combs SE, Heeger S, Haselmann R, et al. Treatment ofprimary glio-blastoma multiforme with cetuximab, radiotherapy and temozolomide (GERT)-phase I/II trial: study protocol. BMC Cancer. 2006;6:133.
85. Diaz Miqueli A, Rolff J, Lemm M, et al. Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies. Br JCancer. 2009;100:950-958.
86. Engelman JA, Zejnullahu K, Gale CM, et al. PF00299804, an irre-versible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res. 2007;67:11924-11932.
87. Wen PY. American Society of Clinical Oncology 2010: report of se-lected studies from the CNS tumors section. Expert Rev Anticancer Ther. 2010;10:1367-1369.
88. George S. Sunitinib, a multitargeted tyrosine kinase inhibitor, in the management ofgastrointestinal stromal tumor. Curr Oncol Rep. 2007; 9:323-327. (Pubitemid 47045167)
89. Nakagawa T, Tohyama O, Yamaguchi A, et al. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010;101: 210-215.
90. Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int JCancer. 2008;122:664-671. (Pubitemid 350308963)
91. Iwamoto FM, Lamborn KR, Robins HI, et al. Phase II trial ofpazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro Oncol. 2010;12:855-861.
92. Reid TS, Beese LS. Crystal structures of the anticancer clinical candi-dates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. Biochem-istry. 2004;43:6877-6884. (Pubitemid 38720505)
93. Awada A, Eskens FA, Piccart M, et al. Phase I and pharmacological study of the oral farnesyltransferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours. Eur J Cancer. 2002;38: 2272-2278. (Pubitemid 35346469)
94. Buonamici S, Williams J, Morrissey M, et al. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in me-dulloblastoma. Sci Transl Med. 2010;2:51ra70.
95. Cloughesy TF, Yoshimoto K, Nghiemphu P, et al. Antitumor activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLo SMed. 2008;5:e8.
96. Plastaras JP, Vapiwala N, Ahmed MS, et al. Validation and toxicity of PI3K/Akt pathway inhibition by HIV protease inhibitors in humans. Cancer Biol Ther. 2008;7:628-635.
97. Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66: 11851-11858. (Pubitemid 46094197)
98. Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition ofcyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor ac-tivity in human tumor xenografts. Mol Cancer Ther. 2004;3: 1427-1438.
99. Jaschinski F, Rothhammer T, Jachimczak P, et al. The antisense oli-gonucleotide Trabedersen (AP 12009) for the targeted inhibition of TGF-beta2. Curr Pharm Biotechnol. [published online ahead of print May 27, 2011].
100. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733-4740.