Promoter hypermethylation of the RB1 gene in glioblastomas.

作者: Mitsutoshi Nakamura , Yasuhiro Yonekawa , Paul Kleihues , Hiroko Ohgaki

DOI: 10.1038/LABINVEST.3780213

关键词:

摘要: Loss of expression the retinoblastoma gene (RB1) has been shown to occur in up 25% glioblastomas (WHO Grade IV). To elucidate underlying mechanism, we assessed RB1 promoter hypermethylation using methylation-specific polymerase chain reaction and by immunohistochemistry 35 primary (de novo) 21 secondary that had progressed from low-grade diffuse astrocytoma II) or anaplastic III). Promoter was significantly more frequent (9 21, 43%) than (5 35, 14%; p = 0.0258). There a clear correlation between loss hypermethylation. In majority with expression, there (11 13, 85%), whereas 93% tumors normal status (p < 0.0001). three glioblastomas, areas without were microdissected; detected only lacking expression. patients multiple biopsies, methylation not detectable less malignant precursor lesions, ie, astrocytoma. These results indicate is late event during progression major mechanism glioblastomas.

参考文章(44)
A. Aoike, N. Ohtani-Fujita, T. Sakai, Paul D Robbins, T. Fujita, N. E. Osifchin, CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene Oncogene. ,vol. 8, pp. 1063- 1067 ,(1993)
J. William Harbour, Douglas C. Dean, Rb function in cell-cycle regulation and apoptosis Nature Cell Biology. ,vol. 2, ,(2000) , 10.1038/35008695
William A. Cliby, Karl C. Podratz, Gary L. Keeney, Karen A. DeLacey, Mark K. Dodson, Robert B. Jenkins, Hong Ji Xu, William F. Benedict, Shi Xue Hu, Jian Li, Evidence of Functional RB Protein in Epithelial Ovarian Carcinomas despite Loss of Heterozygosity at the RB Locus Cancer Research. ,vol. 54, pp. 610- 613 ,(1994)
Steven M Kornblau, Michael Andreeff, Albert B. Deisseroth, Albert B. Deisseroth, Hagop M Kantarjian, Charles Koller, Hong Ji Xu, Elihu Estey, Shilpen Patel, William F Benedict, Shi Xue Hu, Alexandra Theriault, Low and maximally phosphorylated levels of the retinoblastoma protein confer poor prognosis in newly diagnosed acute myelogenous leukemia: a prospective study. Clinical Cancer Research. ,vol. 4, pp. 1955- 1963 ,(1998)
Susan Groshen, Richard J. Cote, John P. Stein, Hong Ji Xu, Clive R. Taylor, Donald G. Skinner, Sunanda J. Chatterjee, Matthew D. Dunn, William F. Benedict, Quoc Chau Tran, Shi Xue Hu, Shan Rong Shi, Elevated and Absent pRb Expression Is Associated with Bladder Cancer Progression and Has Cooperative Effects with p53 Cancer Research. ,vol. 58, pp. 1090- 1094 ,(1998)
Per Alm, Gunilla Sellberg, Qiu-Xia Zhang, Åke Borg, Håkan Olsson, The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression. Cancer Research. ,vol. 52, pp. 2991- 2994 ,(1992)
K Ichimura, Maria Bondesson Bolin, Helena M Goike, Esther E Schmidt, Ahmad Moshref, V Peter Collins, Deregulation of the p14ARF/MDM2/p53 Pathway Is a Prerequisite for Human Astrocytic Gliomas with G1-S Transition Control Gene Abnormalities Cancer Research. ,vol. 60, pp. 417- 424 ,(2000)
Jill A. Macoska, Sofia D. Merajver, Kirk J. Wojno, Kathleen A. Cooney, Timothy P. Singleton, Jon C. Wetzel, Distinct Regions of Allelic Loss on 13q in Prostate Cancer Cancer Research. ,vol. 56, pp. 1142- 1145 ,(1996)
Andreas von Deimling, Jimmy T. Efird, John W. Henson, David N. Louis, Yasuhiro Ono, Keisuke Ueki, CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated Cancer Research. ,vol. 56, pp. 150- 153 ,(1996)
Setsuo Hirohashi, Takao Sekiya, Richard Sachse, Yoshinori Murakami, Hong Ji Xu, Xue Zhang, William F. Benedict, Shi Xue Hu, Kazuo Yashima, Deletions of Chromosome 13q, Mutations in Retinoblastoma 1, and Retinoblastoma Protein State in Human Hepatocellular Carcinoma Cancer Research. ,vol. 54, pp. 4177- 4182 ,(1994)