Abstract
We analyzed DNAs from 35 gliomas (27 malignant, grades III and IV; 8 less malignant, grades I and II) for loss of heterozygosity (LOH) using microsatellite sequences on chromosome 10 as polymorphic markers. An LOH was found in 8 of 11 (73%) glioblastomas (grade IV) and 4 of 16 (25%) grade III gliomas, but not in the less malignant types. We detected three commonly deleted regions. One was located in a telomeric region of 10p and the others were relatively large regions of 10q. Our results suggested that three putative tumor suppressor genes on chromosome 10 are involved in the malignant progression of gliomas.
Keywords: Human glioma, Deletion map, LOH on chromosome 10, Microsatellite sequences, Tumor suppressor gene
Full Text
The Full Text of this article is available as a PDF (263.6 KB).
REFERENCES
- 1. ) Kleihues , P. , Burger , P. C. and Scheithauer , B. W.Histological typing of tumours of the central nervous system. In “ World Health Organization International Histological Classification of Tumours ” ( 1993. ). Springer‐Verlag; , Berlin, Heidelberg . [Google Scholar]
- 2. ) James , C. D. , He , J. , Carlbom , E. , Nordenskjold , M. , Cavenee , W. K. and Collins , V. P.Chromosome 9 deletion mapping reveals interferon α and interferon β‐1 gene deletions in human glioblastomas . Cancer Res. , 51 , 1684 – 1688 ( 1991. ). [PubMed] [Google Scholar]
- 3. ) Olopade , O. I. , Jenkins , R. B. , Ransom , D. T. , Malik , K. , Pomykala , H. , Nobori , T. , Cowan , J. M. , Rowley , J. D. and Diaz , M. O.Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas . Cancer Res. , 52 , 2523 – 2529 ( 1992. ). [PubMed] [Google Scholar]
- 4. ) James , C. D. , Carlbom , E. , Dumanski , J. P. , Hansen , M. , Nordenskjold , M. , Collins , V. P. and Cavenee , W. K.Clonal genomic alterations in glioma malignancy stages . Cancer Res. , 48 , 5546 – 5551 ( 1988. ). [PubMed] [Google Scholar]
- 5. ) Fults , D. , Pedone , C. A. , Thomas , G. A. and White , R.Allelotype of human malignant astrocytoma . Cancer Res. , 50 , 5784 – 5789 ( 1990. ). [PubMed] [Google Scholar]
- 6. ) Ransom , D. T. , Ritland , S. R. , Moertel , C. A. , Dahl , R. J. , O'Fallon , J. R. , Scheithauer , B. W. , Kimmel , D. W. , Kelly , P. J. , Olopade , O. I. , Diaz , M. O. and Jenkins , R. B.Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo‐astrocytomas . Genes Chromosome Cancer , 5 , 357 – 374 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Fults , D. , Petronio , J. , Noblett , B. D. and Pedone , C. A.Chromosome 11p15 deletions in human malignant astrocytomas and primitive neuroectodermal tumors . Genomics , 14 , 799 – 801 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Sonoda , Y. , Iizuka , M. , Yasuda , J. , Makino , R. , Ono , T. , Kayama , T. , Yoshimoto , T. and Sekiya , T.Loss of heterozygosity at 11p15 in malignant glioma . Cancer Res. , 55 , 2166 – 2168 ( 1995. ). [PubMed] [Google Scholar]
- 9. ) Venter , D. J. , Bevan , K. L. , Ludwig , R. L. , Riley , T. E. W. , Jat , P. S. , Thomas , D. G. T. and Noble , M. D.Retinoblastoma gene deletions in human glioblastomas . Oncogene , 6 , 445 – 448 ( 1991. ). [PubMed] [Google Scholar]
- 10. ) James , C. D. , Carlbom , E. , Nordenskjold , M. , Collin , V. P. and Cavenee , W. K.Mitotic recombination of chromosome 17 in astrocytomas . Proc. Natl. Acad. Sci. USA , 86 , 2858 – 2862 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Fults , D. , Tippets , R. H. , Thomas , G. A. , Nakamura , Y. and White , R.Loss of heterozygosity for loci on chromosome 17p in human malignant astrocytoma . Cancer Res. , 49 , 6572 – 6577 ( 1989. ). [PubMed] [Google Scholar]
- 12. ) von Deimling , A. , Louis , D. N. , von Ammon , K. , Petersen , I. , Wiestler , O. D. and Seizinger , B. R.Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas . Cancer Res. , 52 , 4277 – 4279 ( 1992. ). [PubMed] [Google Scholar]
- 13. ) Rey , J. A. , Bello , M. J. , de Campos , J. M. , Vaquero , J. , Kusak , M. E. , Sarasa , J. R. and Peataña , A.Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches . Cancer Genet. Cytogenet. , 66 , 1 – 10 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Frankel , R. H. , Bayona , W. , Koslow , M. and Newcomb , E. W.p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency . Cancer Res. , 52 , 1427 – 1433 ( 1992. ). [PubMed] [Google Scholar]
- 15. ) von Deimling , A. , Eibl , R. H. , Ohgaki , H. , Louis , D. N. , von Ammon , K. , Petersen , I. , Kleihues , P. , Chung , R. Y. , Wiestler , O. D. and Seizinger , B. R.p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma . Cancer Res. , 52 , 2987 – 2990 ( 1992. ). [PubMed] [Google Scholar]
- 16. ) Kamb , A. , Gruis , A. N. , Weaveer‐Feldhaus , J. , Liu , Q. , Harshman , K. , Tavtigian , V. S. , Stockert , E. , Day , S. R. , III , Johnson , E. B. and Skolnick , H. M.A cell cycle regulator potentially involved in genesis of many tumor types . Science , 264 , 436 – 440 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Jen , J. , Harper , W. J. , Binger , S. H. , Binger , D. D. , Papadopoulos , N. , Markowitz , S. , Willson , J. K. V. , Kinzler , W. K. and Vogelstein , B.Deletion of p16 and p15 genes in brain tumors . Cancer Res. , 54 , 6353 – 6358 ( 1994. ). [PubMed] [Google Scholar]
- 18. ) Collins , V. P. and James , C. D.Gene and chromosomal alterations associated with the development of human gliomas . Faseb , 7 , 926 – 930 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Fujimoto , M. , Fults , D. W. , Thomas , G. A. , Nakamura , Y. , Heilbrun , M. P. , White , R. , Story , J. L. , Naylor , S. L. , Kagan‐hallet , K. S. and Sheridan , P. J.Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme . Genomics , 4 , 210 – 214 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Rasheed , B. K. , Fuller , G. N. , Friedman , A. H. , Binger , D. D. and Binger , S. H.Loss of heterozygosity for 10q loci in human glioma . Genes Chromosome Cancer , 5 , 75 – 82 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Fults , D. and Pedone , C. A.Deletion mapping of the long arm of chromosome 10 in glioblastoma multiforme . Genes Chromosome Cancer , 7 , 173 – 177 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Steck , P. A. , Ligon , A. H. , Cheong , P. , Yung , W. K. A. and Pershouse , M. A.Two tumor suppressive loci on chromosome 10 involved in human glioblastoma . Genes Chromosome Cancer , 12 , 255 – 261 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Gyapay , G. , Morissette , J. , Vignal , A. , Dib , C. , Fizames , C. , Millasseau , P. , Marc , S. , Bernardi , G. , Lathrop , M. and Weissenbach , J.The 1993–94 Généthon human genetic linkage map . Nat. Genet. , 7 , 246 – 339 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Rasheed , B. K. A. , Mclendon , R. E. , Friedman , H. S. , Friedman , A. H. , Fuchs , H. E. , Binger , D. D. and Binger , S. H.Chromosome 10 deletion mapping in human gliomas; a common deletion region in 10q25 . Oncogene , 10 , 2243 – 2246 ( 1995. ). [PubMed] [Google Scholar]
- 25. ) Perhouse , M. A. , Stubblefleld , E. , Hadi , A. , Killary , A. M. , Yung , W. K. A. and Steck , P. A.Analysis of the functional role of chromosome 10 in human glioblastomas . Cancer Res. , 53 , 5043 – 5050 ( 1993. ). [PubMed] [Google Scholar]
- 26. ) Bergerheim , U. S. R. , Kunimi , K. , Collins , V. P. and Ekman , P.Deletion mapping of chromosome 8, 10, and 16 in human prostate carcinoma . Genes Chromosome Cancer , 3 , 215 – 220 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 27. ) Kunimi , K. , Bergerheim , U. S. R. , Larsson , I.‐L. , Ekman , P. and Collins , V. P.Allelotyping of human prostatic adenocarchioma . Genomics , 11 , 530 – 536 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 28. ) Carter , B. S. , Ewing , C. M. , Ward , W. S. , Treiger , B. F. , Aalders , T. W. , Schalken , J. A. , Epstein , J. I. and Isaaca , W. B.Allelic losses of chromosome 16q and 10q in human prostate cancer . Proc. Natl. Acad. Sci. USA , 87 , 8751 – 8755 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]