| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology and Genetics |
Departments of Pediatric Hematology/Oncology [B. R. R.] and Pediatric Neurosurgery [H. Z., D. M. W., P. H. C.], Children’s Research Institute, Children’s National Medical Center, Washington, D.C. 20010
Medulloblastoma is the most common malignant brain tumor in children.Chromosome arm 17p13.3 is reduced to homozygosity in 35–50% of medulloblastomas,making it the most frequent genetic alteration in these tumors. HIC-1 (hypermethylated in cancer) is a putative tumor suppressor gene located in the area of common deletion. HIC-1 resides in a CpG island and is hypermethylated in many different tumor types. Therefore, we studied a series of tumor specimens for hypermethylation and deletion of the region containing the HIC-1 gene to determine whether these two mechanisms of gene inactivation play a complimentary role in medulloblastoma. Southern blotting was performed using the methylation-sensitive restriction endonuclease NotI. Methylation of NotI restriction sites located in HIC-1 was demonstrated in 26 (72%) of 36 tumors and 11 (92%) of 12 specimens of normal brain. Of these 26 tumors, 23 differed significantly from normal brain. A greater proportion of the cells from the tumors showed methylated alleles of the HIC-1 gene. A group of 15 (42%) of 36 tumors exhibited loss of heterozygosity (LOH) for DNA sequences located on chromosome arm 17p. There was no significant correlation between LOH and methylation status (P = 0.19). Methylation in tumors beyond that seen in normal brain predicted poor overall survival independent of clinical risk category (P = 0.014). The results of our study show that methylation of the CpG island that contains the HIC-1 gene is common in medulloblastoma and, together with LOH of 17p, may be a critical event in the formation and aggressiveness of this tumor.
This article has been cited by other articles:
|
|
 |
|
  K. J. Briggs, I. M. Corcoran-Schwartz, W. Zhang, T. Harcke, W. L. Devereux, S. B. Baylin, C. G. Eberhart, and D. N. Watkins Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma Genes & Dev., March 15, 2008; 22(6): 770 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pfister, C. Schlaeger, F. Mendrzyk, A. Wittmann, A. Benner, A. Kulozik, W. Scheurlen, B. Radlwimmer, and P. Lichter Array-based profiling of reference-independent methylation status (aPRIMES) identifies frequent promoter methylation and consecutive downregulation of ZIC2 in pediatric medulloblastoma Nucleic Acids Res., April 1, 2007; 35(7): e51 - e51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Packer, A. Gajjar, G. Vezina, L. Rorke-Adams, P. C. Burger, P. L. Robertson, L. Bayer, D. LaFond, B. R. Donahue, M. H. Marymont, et al. Phase III Study of Craniospinal Radiation Therapy Followed by Adjuvant Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma J. Clin. Oncol., September 1, 2006; 24(25): 4202 - 4208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Burzynski, R. A. Weaver, T. Janicki, B. Szymkowski, G. Jurida, M. Khan, and V. Dolgopolov Long-term Survival of High-Risk Pediatric Patients With Primitive Neuroectodermal Tumors Treated With Antineoplastons A10 and AS2-1 Integr Cancer Ther, June 1, 2005; 4(2): 168 - 177. [Abstract] [PDF]
|
|
|
|
 |
|
 W.-C. Xue, K. Y.K. Chan, H.-C. Feng, P.-M. Chiu, H. Y.S. Ngan, S.-W. Tsao, and A. N.Y. Cheung Promoter Hypermethylation of Multiple Genes in Hydatidiform Mole and Choriocarcinoma J. Mol. Diagn., November 1, 2004; 6(4): 326 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pinte, N. Stankovic-Valentin, S. Deltour, B. R. Rood, C. Guerardel, and D. Leprince The Tumor Suppressor Gene HIC1 (Hypermethylated in Cancer 1) Is a Sequence-specific Transcriptional Repressor: DEFINITION OF ITS CONSENSUS BINDING SEQUENCE AND ANALYSIS OF ITS DNA BINDING AND REPRESSIVE PROPERTIES J. Biol. Chem., September 10, 2004; 279(37): 38313 - 38324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Lindsey, M. E. Lusher, J. A. Anderton, S. Bailey, R. J. Gilbertson, A. D.J. Pearson, D. W. Ellison, and S. C. Clifford Identification of tumour-specific epigenetic events in medulloblastoma development by hypermethylation profiling Carcinogenesis, May 1, 2004; 25(5): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Fisher, P. C. Burger, and C. G. Eberhart Biologic Risk Stratification of Medulloblastoma: The Real Time Is Now J. Clin. Oncol., March 15, 2004; 22(6): 971 - 974. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rathi, A. K. Virmani, K. Harada, C. F. Timmons, K. Miyajima, R. J. Hay, D. Mastrangelo, A. Maitra, G. E. Tomlinson, and A. F. Gazdar Aberrant Methylation of the HIC1 Promoter Is a Frequent Event in Specific Pediatric Neoplasms Clin. Cancer Res., September 1, 2003; 9(10): 3674 - 3678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. MacDonald, B. R. Rood, M. R. Santi, G. Vezina, K. Bingaman, P. H. Cogen, and R. J. Packer Advances in the Diagnosis, Molecular Genetics, and Treatment of Pediatric Embryonal CNS Tumors Oncologist, April 1, 2003; 8(2): 174 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Wechsler-Reya Analysis of Gene Expression in the Normal and Malignant Cerebellum Recent Prog. Horm. Res., January 1, 2003; 58(1): 227 - 248. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
