| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Ludwig Institute for Cancer Research, Montreal, Canada [C. D. J., M. H., W. K. C.]; Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden [E. C.]; Ludwig Institute for Cancer Research, Stockholm, Sweden [V. P. C., J. P. D.]; and Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden [M. N.]
Comparison of constitutional and tumor genotypes at chromosomal loci defined by restriction fragment length alleles has proven useful in determining the genomic position and tissue specificity of recessive mutations that predispose to cancer (Hansen, M. F., and Cavenee, W. K. Cancer Res., 47: 5518–5527, 1987). Here we have applied this approach to 53 unrelated patients with glial tumors of varying histological malignancy grade. Loss of constitutional heterozygosity for loci on chromosome 10 was observed in 28 of 29 tumors histologically classified as glioblastoma (malignancy grade IV) whereas no similar losses were observed in any of 22 gliomas of lower malignancy grade. Examination of restriction fragment length alleles on other chromosomes revealed that loss of sequences on chromosomes 13, 17, or 22 had occurred at nonrandom frequencies and in at least one instance of each malignancy grade of adult glioma. The tumors in which loss of constitutional heterozygosity was observed were composed of one or a mixture of glial cell subtypes displaying astrocytic, oligodendrocytic, and/or ependymal differentiation. These results demonstrate a close association of the loss of chromosome 10 sequences with the most malignant histological stage of glioma and that glioblastoma arises as the clonal expansion of an earlier staged precursor. Furthermore they suggest that glioblastoma is a common phenotypic and malignancy terminus for glial tumors of various cellular subtypes which is reached through a common molecular pathway. This approach which involves the identification of malignancy stage specific somatic losses of heterozygosity provides a genotypic, rather than phenotypic, analysis of tumor progression.
1 This work was supported in part by grants from the Swedish Cancer Society, IngaBritt and Arne Lundbergs Research Foundation, and the Swedish Work Environment Fund.
2 To whom requests for reprints should be addressed, at Ludwig Institute for Cancer Research, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Canada H3A 1A1.
Received 6/ 7/88. Revised 7/25/88. Accepted 7/27/88.
This article has been cited by other articles:
|
|
 |
|
  F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment Genes & Dev., November 1, 2007; 21(21): 2683 - 2710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Giannini, J. N. Sarkaria, A. Saito, J. H. Uhm, E. Galanis, B. L. Carlson, M. A. Schroeder, and C. D. James Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme Neuro-oncol, April 1, 2005; 7(2): 164 - 176. [Abstract] [PDF]
|
|
|
|
 |
|
 V P Collins Brain tumours: classification and genes J. Neurol. Neurosurg. Psychiatry, June 1, 2004; 75(suppl_2): ii2 - ii11. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mihaila, J. A. Gutierrez, M. L. Rosenblum, I. F. Newsham, O. Bogler, and S. A. Rempel Meningiomas: Analysis of Loss of Heterozygosity on Chromosome 10 in Tumor Progression and the Delineation of Four Regions of Chromosomal Deletion in Common with Other Cancers Clin. Cancer Res., October 1, 2003; 9(12): 4435 - 4442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. F. Lang, M. R. Gilbert, V. K. Puduvalli, J. Weinberg, V. A. Levin, W.K. A. Yung, R. Sawaya, G. N. Fuller, and C. A. Conrad Toward better early-phase brain tumor clinical trials: A reappraisal of current methods and proposals for future strategies Neuro-oncol, October 1, 2002; 4(4): 268 - 277. [Abstract] [PDF]
|
|
|
|
|
|
G. D. Eley, J. L. Reiter, A. Pandita, S. Park, R. B. Jenkins, N. J. Maihle, and C. D. James A chromosomal region 7p11.2 transcript map: Its development and application to the study of EGFR amplicons in glioblastoma Neuro-oncol, April 1, 2002; 4(2): 86 - 94. [Abstract] [PDF]
|
|
|
|
 |
|
 I. F. Pollack, S. D. Finkelstein, J. Woods, J. Burnham, E. J. Holmes, R. L. Hamilton, A. J. Yates, J. M. Boyett, J. L. Finlay, R. Sposto, et al. Expression of p53 and Prognosis in Children with Malignant Gliomas N. Engl. J. Med., February 7, 2002; 346(6): 420 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. F. Pollack, S. D. Finkelstein, J. Burnham, E. J. Holmes, R. L. Hamilton, A. J. Yates, J. L. Finlay, and R. Sposto Age and TP53 Mutation Frequency in Childhood Malignant Gliomas: Results in a Multi-institutional Cohort Cancer Res., October 1, 2001; 61(20): 7404 - 7407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Maher, F. B. Furnari, R. M. Bachoo, D. H. Rowitch, D. N. Louis, W. K. Cavenee, and R. A. DePinho Malignant glioma: genetics and biology of a grave matter Genes & Dev., June 1, 2001; 15(11): 1311 - 1333. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Nigro, M. A. Takahashi, D. G. Ginzinger, M. Law, S. Passe, R. B. Jenkins, and K. Aldape Detection of 1p and 19q Loss in Oligodendroglioma by Quantitative Microsatellite Analysis, a Real-Time Quantitative Polymerase Chain Reaction Assay Am. J. Pathol., April 1, 2001; 158(4): 1253 - 1262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Frederick, G. Eley, X.-Y. Wang, and C. D. James Analysis of genomic rearrangements associated with EGFRvIII expression suggests involvement of Alu repeat elements Neuro-oncol, July 1, 2000; 2(3): 159 - 163. [Abstract] [PDF]
|
|
|
|
|
|
R. N. Wiltshire, B.K. A. Rasheed, H. S. Friedman, A. H. Friedman, and S. H. Bigner Comparative genetic patterns of glioblastoma multiforme: Potential diagnostic tool for tumor classification Neuro-oncol, July 1, 2000; 2(3): 164 - 173. [Abstract] [PDF]
|
|
|
|
|
|
L. Frederick, X.-Y. Wang, G. Eley, and C. D. James Diversity and Frequency of Epidermal Growth Factor Receptor Mutations in Human Glioblastomas Cancer Res., March 1, 2000; 60(5): 1383 - 1387. [Abstract] [Full Text]
|
|
|
|
|
|
D. J. Brat, C. D. James, A. E. Jedlicka, D. C. Connolly, E. Chang, R. J. Castellani, M. Schmid, M. Schiller, D. A. Carson, and P. C. Burger Molecular Genetic Alterations in Radiation-Induced Astrocytomas Am. J. Pathol., May 1, 1999; 154(5): 1431 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Couch, X.-Y. Wang, G.-J. Wu, J. Qian, R. B. Jenkins, and C. D. James Localization of PS6K to Chromosomal Region 17q23 and Determination of Its Amplification in Breast Cancer Cancer Res., April 1, 1999; 59(7): 1408 - 1411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Ward, G. Brenta, M. Medvedovic, and J. A. Fagin Studies of Allelic Loss in Thyroid Tumors Reveal Major Differences in Chromosomal Instability between Papillary and Follicular Carcinomas J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 525 - 530. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. B. Furnari, H. Lin, H.-J. S. Huang, and W. K. Cavenee Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain PNAS, November 11, 1997; 94(23): 12479 - 12484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. O'Rourke, X. Qian, H.-T. Zhang, J. G. Davis, E. Nute, J. Meinkoth, and M. I. Greene Trans receptor inhibition of human glioblastoma cells by erbB family ectodomains PNAS, April 1, 1997; 94(7): 3250 - 3255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Bates, W. E. Farrell, E. J. Bicknell, A. M. McNicol, A. J. Talbot, J. C. Broome, C. W. Perrett, R. V. Thakker, and R. N. Clayton Allelic Deletion in Pituitary Adenomas Reflects Aggressive Biological Activity and Has Potential Value as a Prognostic Marker J. Clin. Endocrinol. Metab., March 1, 1997; 82(3): 818 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-K. Ng, M. Phil, K.-W. Lo, D. P. Huang, and W.-S. Poon p53 in Low-grade Gliomas International Journal of Surgical Pathology, January 1, 1994; 1(3): 163 - 170. [Abstract] [PDF]
|
|
|
|
 |
|
 E Solomon, J Borrow, and A. Goddard Chromosome aberrations and cancer Science, November 22, 1991; 254(5035): 1153 - 1160. [Abstract] [PDF]
|
|
|
|
|
|
S. Baker, S Markowitz, E. Fearon, J. Willson, and B Vogelstein Suppression of human colorectal carcinoma cell growth by wild-type p53 Science, August 24, 1990; 249(4971): 912 - 915. [Abstract] [PDF]
|
|
|
|
|
|
S. Baker, E. Fearon, J. Nigro, Hamilton SR, A. Preisinger, J. Jessup, P vanTuinen, D. Ledbetter, D. Barker, Y Nakamura, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas Science, April 14, 1989; 244(4901): 217 - 221. [Abstract] [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 |
