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Targeting Brain Cancer: Advances In The Molecular Pathology Of Malignant Glioma And Medulloblastoma
Stupp, R. Et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987–996 (2005).
Wen, P. Y. & Kesari, S. Malignant gliomas in adults. N. Engl. J. Med. 359, 492–507 (2008).
Gilbertson, R. J. Medulloblastoma: signalling a change in treatment. Lancet Oncol. 5, 209–218 (2004).
Bailey, P. & Cushing, H. A Classification of Tumoursof the Glioma Group on a Histogenic Basis (J. B Lippincott, Philadelphia, 1926).
Kernohan, J. W., Mabon, R. F. & Svien, H. J. A simplified classification of gliomas. Proc. Staff Meetings Mayo Clinic 24, 71–74 (1949).
Ringertz, N. Grading of gliomas. Acta Pathol Microbiol Scand. 27, 51–65 (1950).
Zülch, K. J. (ed.) Histological typing of tumours of the central nervous system (World Health Organization, Switzerland, 1979).
Louis, D. N. Et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114, 97–109 (2007). This paper establishes the current morphological and molecular criteria for the subclassification of brain tumours.
Dropcho, E. J. & Soong, S. J. The prognostic impact of prior low grade histology in patients with anaplastic gliomas: a case-control study. Neurology 47, 684–690 (1996).
Ohgaki, H. & Kleihues, P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J. Neuropathol. Exp. Neurol. 64, 479–489 (2005).
Ohgaki, H. Et al. A case history of glioma progression. Acta Neuropathol. 97, 525–532 (1999).
Scherer, H. J. Cerebral astrocytomas and their derivatives. Am. J. Cancer 40, 159–198 (1940).
Rutkowski, S. Et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N. Engl. J. Med. 352, 978–986 (2005).
Sure, U. Et al. Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute. Acta Neurochir. (Wien) 132, 59–65 (1995).
Brown, H. G. Et al. "Large cell/anaplastic" medulloblastomas: a Pediatric Oncology Group Study. J. Neuropathol. Exp. Neurol. 59, 857–865 (2000).
Giangaspero, F. Et al. Large-cell medulloblastomas. A distinct variant with highly aggressive behavior. Am. J. Surg. Pathol. 16, 687–693 (1992).
Giangaspero, F. Et al. Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol. 112, 5–12 (2006).
McManamy, C. S. Et al. Morphophenotypic variation predicts clinical behavior in childhood non-desmoplastic medulloblastomas. J. Neuropathol. Exp. Neurol. 62, 627–632 (2003).
Malkin, D. Et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250, 1233–1238 (1990).
Srivastava, S., Zou, Z. Q., Pirollo, K., Blattner, W. & Chang, E. H. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348, 747–749 (1990).
Louis, D. N. The p53 gene and protein in human brain tumors. J. Neuropathol. Exp. Neurol. 53, 11–21 (1994).
Libermann, T. A. Et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313, 144–147 (1985).
Libermann, T. A. Et al. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res. 44, 753–760 (1984).
Wong, A. J. Et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc. Natl Acad. Sci. USA 89, 2965–2969 (1992).
Frederick, L., Wang, X. Y., Eley, G. & James, C. D. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res. 60, 1383–1387 (2000).
Sugawa, N., Ekstrand, A. J., James, C. D. & Collins, V. P. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc. Natl Acad. Sci. USA 87, 8602–8606 (1990).
Cairncross, J. G. Et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J. Natl Cancer Inst. 90, 1473–1479 (1998).
Reifenberger, G. Et al. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am. J. Pathol. 145, 1175–1190 (1994).
Smith, J. S. Et al. Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18, 4144–4152 (1999).
Barbashina, V., Salazar, P., Holland, E. C., Rosenblum, M. K. & Ladanyi, M. Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene. Clin. Cancer Res. 11, 1119–1128 (2005).
Costello, J. F. Et al. Cyclin-dependent kinase 6 (CDK6) amplification in human gliomas identified using two-dimensional separation of genomic DNA. Cancer Res. 57, 1250–1254 (1997).
Henson, J. W. Et al. The retinoblastoma gene is involved in the malignant progression of astrocytomas. Ann. Neurol. 36, 714–721 (1994).
Reifenberger, G., Reifenberger, J., Ichimura, K., Meltzer, P. S. & Collins, V. P. Amplification of multiple genes from chromosomal region 12q13–14 in human malignant gliomas: preliminary mapping of the amplicons shows preferential involvement of CDK4, SAS, and MDM2. Cancer Res. 54, 4299–4303 (1994).
Watanabe, T. Et al. Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendroglioma. J. Neuropathol. Exp. Neurol. 60, 1181–1190 (2001).
Shete, S. Et al. Genome-wide association study identifies five susceptibility loci for glioma. Nature Genet. 41, 899–904 (2009).
Wrensch, M. Et al. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nature Genet. 41, 905–908 (2009). References 35 and 36 are large genome-wide association screens identifying low-penetrance susceptibility alleles that increase glioma risk.
Dai, C. Et al. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev. 15, 1913–1925 (2001).
Hu, X. Et al. MTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma. Neoplasia 7, 356–368 (2005).
Uhrbom, L., Nerio, E. & Holland, E. C. Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nature Med. 10, 1257–1260 (2004).
Marino, S., Vooijs, M., van Der Gulden, H., Jonkers, J. & Berns, A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 14, 994–1004 (2000).
Reilly, K. M., Loisel, D. A., Bronson, R. T., McLaughlin, M. E. & Jacks, T. Nf1; Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nature Genet. 26, 109–113 (2000).
Weiss, W. A. Et al. Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res. 63, 1589–1595 (2003).
Xiao, A., Wu, H., Pandolfi, P. P., Louis, D. N. & Van Dyke, T. Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell 1, 157–168 (2002).
Xiao, A. Et al. Somatic induction of Pten loss in a preclinical astrocytoma model reveals major roles in disease progression and avenues for target discovery and validation. Cancer Res. 65, 5172–5180 (2005).
Zheng, H. Et al. P53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature 455, 1129–1133 (2008).
Zhu, Y. Et al. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8, 119–130 (2005).
Di Rocco, F., Carroll, R. S., Zhang, J. & Black, P. M. Platelet-derived growth factor and its receptor expression in human oligodendrogliomas. Neurosurgery 42, 341–346 (1998).
Westermark, B., Heldin, C. H. & Nister, M. Platelet-derived growth factor in human glioma. Glia 15, 257–263 (1995).
Clarke, I. D. & Dirks, P. B. A human brain tumor-derived PDGFR-α deletion mutant is transforming. Oncogene 22, 722–733 (2003).
Abounader, R. & Laterra, J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol. 7, 436–451 (2005).
Guha, A., Feldkamp, M. M., Lau, N., Boss, G. & Pawson, A. Proliferation of human malignant astrocytomas is dependent on Ras activation. Oncogene 15, 2755–2765 (1997).
Wang, H. Et al. Analysis of the activation status of Akt, NFkB, and Stat3 in human diffuse gliomas. Lab. Invest. 84, 941–951 (2004).
James, C. D. Et al. Clonal genomic alterations in glioma malignancy stages. Cancer Res. 48, 5546–5551 (1988).
Ding, H. Et al. Oligodendrogliomas result from the expression of an activated mutant epidermal growth factor receptor in a RAS transgenic mouse astrocytoma model. Cancer Res. 63, 1106–1113 (2003).
Shih, A. H. Et al. Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis. Cancer Res. 64, 4783–4789 (2004).
Uhrbom, L. Et al. Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt. Cancer Res. 62, 5551–5558 (2002).
Uhrbom, L., Hesselager, G., Nister, M. & Westermark, B. Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. Cancer Res. 58, 5275–5279 (1998).
Wei, Q. Et al. High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model. Cancer Res. 66, 7429–7437 (2006).
Zhu, H. Et al. Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc. Natl Acad. Sci. USA 106, 2712–2716 (2009).
Ding, H. Et al. Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas. Cancer Res. 61, 3826–3836 (2001).
Holland, E. C. Et al. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nature Genet. 25, 55–57 (2000).
Kwon, C. H. Et al. Pten haploinsufficiency accelerates formation of high-grade astrocytomas. Cancer Res. 68, 3286–3294 (2008).
Llaguno, S. A. Et al. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15, 45–56 (2009).
Burton, E. C. Et al. Genetic aberrations defined by comparative genomic hybridization distinguish long-term from typical survivors of glioblastoma. Cancer Res. 62, 6205–6210 (2002).
Hui, A. B., Lo, K. W., Yin, X. L., Poon, W. S. & Ng, H. K. Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization. Lab. Invest. 81, 717–723 (2001).
Maher, E. A. Et al. Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. Cancer Res. 66, 11502–11513 (2006).
Misra, A. Et al. Array comparative genomic hybridization identifies genetic subgroups in grade 4 human astrocytoma. Clin. Cancer Res. 11, 2907–2918 (2005).
The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008). This study reports large-scale, integrated genomic analysis revealing the central importance of certain core signalling pathways in the pathogenesis of malignant glioma.
Nigro, J. M. Et al. Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma. Cancer Res. 65, 1678–1686 (2005).
Nishizaki, T. Et al. Clinical evidence of distinct subgroups of astrocytic tumors defined by comparative genomic hybridization. Hum. Pathol. 31, 608–614 (2000).
Parsons, D. W. Et al. An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807–1812 (2008). This study reached many of the same conclusions as reference 68 but also identified pathogenic mutations in IDH1.
Bredel, M. Et al. A network model of a cooperative genetic landscape in brain tumors. JAMA 302, 261–275 (2009).
Yan, H. Et al. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360, 765–773 (2009).
Hartmann, C. Et al. 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 (2009).
Sanson, M. Et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J. Clin. Oncol. 27, 4150–4154 (2009).
Zhao, S. Et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α. Science 324, 261–265 (2009). This study identifies a potential pathogenic mechanism for mutations in IDH proteins relating to a loss of enzymatic function.
Jensen, R. L. Brain tumor hypoxia: tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target. J. Neurooncol. 92, 317–335 (2009).
Dang, L. Et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462, 739–744 (2009). This study identifies the abnormal production of 2-HG as a potential pathogenic mechanism for IDH mutations in glioma.
Mardis, E. R. Et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 361, 1058–1066 (2009).
Huse, J. T. Et al. The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev. 23, 1327–1337 (2009).
Kim, H. Et al. Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. Proc. Natl Acad. Sci. USA 107, 2183–2188 (2010).
Li, Y. Et al. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 69, 7569–7576 (2009).
Novakova, J., Slaby, O., Vyzula, R. & Michalek, J. MicroRNA involvement in glioblastoma pathogenesis. Biochem. Biophys. Res. Commun. 386, 1–5 (2009).
Godard, S. Et al. Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Res. 63, 6613–6625 (2003).
Nutt, C. L. Et al. Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res. 63, 1602–1607 (2003).
Li, A. Et al. Unsupervised analysis of transcriptomic profiles reveals six glioma subtypes. Cancer Res. 69, 2091–2099 (2009).
Liang, Y. Et al. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc. Natl Acad. Sci. USA 102, 5814–5819 (2005).
Phillips, H. S. Et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9, 157–173 (2006). This study uses transcriptional profiling to subdivide malignant gliomas into distinct categories that differ in their neurobiological characteristics and clinical prognoses.
Horvath, S. Et al. Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proc. Natl Acad. Sci. USA 103, 17402–17407 (2006).
Brennan, C. Et al. Glioblastoma subclasses can be defined by activity among signal transduction pathways and associated genomic alterations. PLoS ONE 4, e7752 (2009). This study uses an integrated genomics analysis of TCGA data coupled with proteomics in a second large tumour set to link glioma transcriptional subclasses with defined core signalling abnormalities.
Verhaak, R. G. W. Et al. An integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98–110 (2009). This study uses TCGA data and an integrated genomics approach to associate glioma transcriptional subclasses with distinct abnormalities in specific genes.
Carro, M. S. Et al. The transcriptional network for mesenchymal transformation of brain tumours. Nature 463, 318–325 (2010).
Entz-Werle, N. Et al. Medulloblastoma: what is the role of molecular genetics? Expert Rev. Anticancer Ther. 8, 1169–1181 (2008).
Pietsch, T. Et al. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res. 57, 2085–2088 (1997).
Raffel, C. Et al. Sporadic medulloblastomas contain PTCH mutations. Cancer Res. 57, 842–845 (1997).
Reifenberger, J. Et al. Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 58, 1798–1803 (1998).
Taylor, M. D. Et al. Mutations in SUFU predispose to medulloblastoma. Nature Genet. 31, 306–310 (2002).
Hahn, H. Et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85, 841–851 (1996).
Pomeroy, S. L. & Sturla, L. M. Molecular biology of medulloblastoma therapy. Pediatr. Neurosurg. 39, 299–304 (2003).
Schuller, U. Et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14, 123–134 (2008).
Yang, Z. J. Et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14, 135–145 (2008).
Browd, S. R. Et al. N-myc can substitute for insulin-like growth factor signaling in a mouse model of sonic hedgehog-induced medulloblastoma. Cancer Res. 66, 2666–2672 (2006).
Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113 (1997).
Hallahan, A. R. Et al. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res. 64, 7794–7800 (2004).
Hatton, B. A. Et al. The Smo/Smo model: hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread. Cancer Res. 68, 1768–1776 (2008).
Lee, Y. Et al. Patched2 modulates tumorigenesis in patched1 heterozygous mice. Cancer Res. 66, 6964–6971 (2006).
McCall, T. D., Pedone, C. A. & Fults, D. W. Apoptosis suppression by somatic cell transfer of Bcl-2 promotes Sonic hedgehog-dependent medulloblastoma formation in mice. Cancer Res. 67, 5179–5185 (2007).
Pazzaglia, S. Et al. High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice. Oncogene 21, 7580–7584 (2002).
Pazzaglia, S. Et al. Linking DNA damage to medulloblastoma tumorigenesis in patched heterozygous knockout mice. Oncogene 25, 1165–1173 (2006).