| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Pathology,*
Surgery,
and Radiation
Oncology,§
and the Hereditary Gastrointestinal
Cancer Registry,
Queen Mary Hospital, The
University of Hong Kong, Hong Kong
Microsatellite instability (MSI) has been identified in various human cancers, particularly those associated with the hereditary nonpolyposis colorectal cancer syndrome. Although gliomas have been reported in a few hereditary nonpolyposis colorectal cancer syndrome kindred, data on the incidence of MSI in gliomas are conflicting, and the nature of the mismatch repair (MMR) defect is not known. We established the incidence of MSI and the underlying MMR gene mutation in 22 patients ages 45 years or less with sporadic high-grade gliomas (17 glioblastomas, 3 anaplastic astrocytomas, and 2 mixed gliomas, grade III). Using five microsatellite loci, four patients (18%) had high level MSI, with at least 40% unstable loci. Germline MMR gene mutation was detected in all four patients, with inactivation of the second allele of the corresponding MMR gene or loss of protein expression in the tumor tissue. Frameshift mutation in the mononucleotide tract of insulin-like growth factor type II receptor was found in one high-level MSI glioma, but none was found in the transforming growth factor ß type II receptor and the Bax genes. There was no family history of cancer in three of the patients, and although one patient did have a family history of colorectal carcinoma, the case did not satisfy the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome. Three patients developed metachronous colorectal adenocarcinomas, fitting the criteria of Turcot's syndrome. Thus, MSI and germline MMR gene mutation is present in a subset of young glioma patients, and these patients and their family members are at risk of developing other hereditary nonpolyposis colorectal cancer syndrome-related tumors, in particular colorectal carcinomas. These results have important implications in the genetic testing and management of young patients with glioma and their families.
This article has been cited by other articles:
 |
|
 |
|
  H. Feitsma, R. V. Kuiper, J. Korving, I. J. Nijman, and E. Cuppen Zebrafish with Mutations in Mismatch Repair Genes Develop Neurofibromas and Other Tumors Cancer Res., July 1, 2008; 68(13): 5059 - 5066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Gammie, N. Erdeniz, J. Beaver, B. Devlin, A. Nanji, and M. D. Rose Functional Characterization of Pathogenic Human MSH2 Missense Mutations in Saccharomyces cerevisiae Genetics, October 1, 2007; 177(2): 707 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Fukushima, Y. Katayama, T. Watanabe, A. Yoshino, A. Ogino, T. Ohta, and C. Komine Promoter Hypermethylation of Mismatch Repair Gene hMLH1 Predicts the Clinical Response of Malignant Astrocytomas to Nitrosourea Clin. Cancer Res., February 15, 2005; 11(4): 1539 - 1544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Broniscer and A. Gajjar Supratentorial High-Grade Astrocytoma and Diffuse Brainstem Glioma: Two Challenges for the Pediatric Oncologist Oncologist, April 1, 2004; 9(2): 197 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hirose, M. Katayama, D. Stokoe, D. A. Haas-Kogan, M. S. Berger, and R. O. Pieper The p38 Mitogen-Activated Protein Kinase Pathway Links the DNA Mismatch Repair System to the G2 Checkpoint and to Resistance to Chemotherapeutic DNA-Methylating Agents Mol. Cell. Biol., November 15, 2003; 23(22): 8306 - 8315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Stark, P Witzel, R J Strege, H-H Hugo, and H M Mehdorn p53, mdm2, EGFR, and msh2 expression in paired initial and recurrent glioblastoma multiforme J. Neurol. Neurosurg. Psychiatry, June 1, 2003; 74(6): 779 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirose, M. S. Berger, and R. O. Pieper Abrogation of the Chk1-mediated G2 Checkpoint Pathway Potentiates Temozolomide-induced Toxicity in a p53-independent Manner in Human Glioblastoma Cells Cancer Res., August 1, 2001; 61(15): 5843 - 5849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirose, M. S. Berger, and R. O. Pieper p53 Effects Both the Duration of G2/M Arrest and the Fate of Temozolomide-treated Human Glioblastoma Cells Cancer Res., March 1, 2001; 61(5): 1957 - 1963. [Abstract] [Full Text]
|
|
|
|
|
|
M. Alonso, R. Hamelin, M. Kim, K. Porwancher, T. Sung, P. Parhar, D. C. Miller, and E. W. Newcomb Microsatellite Instability Occurs in Distinct Subtypes of Pediatric but not Adult Central Nervous System Tumors Cancer Res., March 1, 2001; 61(5): 2124 - 2128. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. L. Chan, S. T. Yuen, L. P. Chung, J. W. C. Ho, K. Y. M. Kwan, A. S. Y. Chan, J. C. Y. Ho, S. Y. Leung, and A. H. Wyllie Frequent Microsatellite Instability and Mismatch Repair Gene Mutations in Young Chinese Patients With Colorectal Cancer J Natl Cancer Inst, July 21, 1999; 91(14): 1221 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Falls, D. J. Pulford, A. A. Wylie, and R. L. Jirtle Genomic Imprinting: Implications for Human Disease Am. J. Pathol., March 1, 1999; 154(3): 635 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Leung, S. T. Yuen, L. P. Chung, K. M. Chu, A. S. Y. Chan, and J. C. I. Ho hMLH1 Promoter Methylation and Lack of hMLH1 Expression in Sporadic Gastric Carcinomas with High-Frequency Microsatellite Instability Cancer Res., January 1, 1999; 59(1): 159 - 164. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
