Development and Cancer of the Cerebellum

Overview

Journal Trends Neurosci

Specialty Neurology

Date 2011 Feb 15

PMID 21315459

Citations 90

Authors

Mary E Hatten

Martine F Roussel

Affiliations

Soon will be listed here.

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor and is thought to arise from genetic anomalies in developmental pathways required for the normal maturation of the cerebellar cortex, notably developmental pathways for granule cell progenitor (GCP) neurogenesis. Over the past decade, a wide range of studies have identified genes and their regulators within signaling pathways, as well as noncoding RNAs, that have crucial roles in both normal cerebellar development and pathogenesis. These include the Notch, Wnt/β-catenin, bone morphogenic proteins (Bmp) and Sonic Hedgehog (Shh) pathways. In this review, we highlight the function of these pathways in the growth of the cerebellum and the formation of MB. A better understanding of the developmental origins of these tumors will have significant implications for enhancing the treatment of this important childhood cancer.

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References

Fink A, Englund C, Daza R, Pham D, Lau C, Nivison M . Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip. J Neurosci. 2006; 26(11):3066-76. PMC: 6673970. DOI: 10.1523/JNEUROSCI.5203-05.2006. View

Ellison D, Onilude O, Lindsey J, Lusher M, Weston C, Taylor R . beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee. J Clin Oncol. 2005; 23(31):7951-7. DOI: 10.1200/JCO.2005.01.5479. View

De Zeeuw C, Yeo C . Time and tide in cerebellar memory formation. Curr Opin Neurobiol. 2005; 15(6):667-74. DOI: 10.1016/j.conb.2005.10.008. View

Wingate R . The rhombic lip and early cerebellar development. Curr Opin Neurobiol. 2001; 11(1):82-8. DOI: 10.1016/s0959-4388(00)00177-x. View

Boyden E, Katoh A, Raymond J . Cerebellum-dependent learning: the role of multiple plasticity mechanisms. Annu Rev Neurosci. 2004; 27:581-609. DOI: 10.1146/annurev.neuro.27.070203.144238. View

Gibson P, Tong Y, Robinson G, Thompson M, Currle D, Eden C . Subtypes of medulloblastoma have distinct developmental origins. Nature. 2010; 468(7327):1095-9. PMC: 3059767. DOI: 10.1038/nature09587. View

Fan X, Mikolaenko I, Elhassan I, Ni X, Wang Y, Ball D . Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 2004; 64(21):7787-93. DOI: 10.1158/0008-5472.CAN-04-1446. View

Eberhart C, Kratz J, Wang Y, Summers K, Stearns D, Cohen K . Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004; 63(5):441-9. DOI: 10.1093/jnen/63.5.441. View

Merchant T, Kun L, Krasin M, Wallace D, Chintagumpala M, Woo S . Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma. Int J Radiat Oncol Biol Phys. 2007; 70(3):782-7. PMC: 2716663. DOI: 10.1016/j.ijrobp.2007.07.2342. View

10.

Joyner A . Engrailed, Wnt and Pax genes regulate midbrain--hindbrain development. Trends Genet. 1996; 12(1):15-20. DOI: 10.1016/0168-9525(96)81383-7. View

11.

Yauch R, Dijkgraaf G, Alicke B, Januario T, Ahn C, Holcomb T . Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009; 326(5952):572-4. PMC: 5310713. DOI: 10.1126/science.1179386. View

12.

Brugieres L, Pierron G, Chompret A, Bressac-de Paillerets B, Di Rocco F, Varlet P . Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations. J Med Genet. 2009; 47(2):142-4. DOI: 10.1136/jmg.2009.067751. View

13.

Hallahan A, Pritchard J, Hansen S, Benson M, Stoeck J, Hatton B . The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res. 2004; 64(21):7794-800. DOI: 10.1158/0008-5472.CAN-04-1813. View

14.

Agger K, Cloos P, Christensen J, Pasini D, Rose S, Rappsilber J . UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature. 2007; 449(7163):731-4. DOI: 10.1038/nature06145. View

15.

Zindy F, Knoepfler P, Xie S, Sherr C, Eisenman R, Roussel M . N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development. Proc Natl Acad Sci U S A. 2006; 103(31):11579-83. PMC: 1518798. DOI: 10.1073/pnas.0604727103. View

16.

Rudin C, Hann C, Laterra J, Yauch R, Callahan C, Fu L . Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med. 2009; 361(12):1173-8. PMC: 5317279. DOI: 10.1056/NEJMoa0902903. View

17.

Alvarez-Rodriguez R, Barzi M, Berenguer J, Pons S . Bone morphogenetic protein 2 opposes Shh-mediated proliferation in cerebellar granule cells through a TIEG-1-based regulation of Nmyc. J Biol Chem. 2007; 282(51):37170-80. DOI: 10.1074/jbc.M705414200. View

18.

Goodrich L, Milenkovic L, Higgins K, Scott M . Altered neural cell fates and medulloblastoma in mouse patched mutants. Science. 1997; 277(5329):1109-13. DOI: 10.1126/science.277.5329.1109. View

19.

Nakahara Y, Northcott P, Li M, Kongkham P, Smith C, Yan H . Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma. Neoplasia. 2010; 12(1):20-7. PMC: 2805880. DOI: 10.1593/neo.91122. View

20.

Uziel T, Karginov F, Xie S, Parker J, Wang Y, Gajjar A . The miR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci U S A. 2009; 106(8):2812-7. PMC: 2636735. DOI: 10.1073/pnas.0809579106. View