Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Jan 18;82(3):543–549. doi: 10.1054/bjoc.1999.0961

Multiple deleted regions on the long arm of chromosome 6 in astrocytic tumours

A Miyakawa 1,2,3,4, K Ichimura 1,2, E E Schmidt 1,2, S Varmeh-Ziaie 1,2, V P Collins 1,2
PMCID: PMC2363324  PMID: 10682663

Abstract

Chromosome 6 deletions are common in human neoplasms including gliomas. In order to study the frequency and identify commonly deleted regions of chromosome 6 in astrocytomas, 159 tumours (106 glioblastomas, 39 anaplastic astrocytomas and 14 astrocytomas malignancy grade II) were analysed using 31 microsatellite markers that span the chromosome. Ninety-five per cent of cases with allelic losses had losses affecting 6q. Allelic losses were infrequent in astrocytomas malignancy grade II (14%) but more usual in anaplastic astrocytomas (38%) and glioblastomas (37%). Evidence for clonal heterogeneity in the astrocytomas and anaplastic astrocytomas was frequently observed (i.e. co-existence of subpopulations with and without chromosome 6 deletions). Clonal heterogeneity was less common in glioblastomas. Five commonly deleted regions were identified on 6q. These observations suggest that a number of tumour suppressor genes are located on 6q and that these genes may be involved in the progression of astrocytic tumours. © 2000 Cancer Research Campaign

Keywords: astrocytoma, glioblastoma, microsatellite analysis, allelic loss, tumour progression, clonal heterogeneity

Full Text

The Full Text of this article is available as a PDF (225.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abdollahi A., Roberts D., Godwin A. K., Schultz D. C., Sonoda G., Testa J. R., Hamilton T. C. Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in development of many solid tumors. Oncogene. 1997 Apr 24;14(16):1973–1979. doi: 10.1038/sj.onc.1201034. [DOI] [PubMed] [Google Scholar]
  2. Banga S. S., Kim S., Hubbard K., Dasgupta T., Jha K. K., Patsalis P., Hauptschein R., Gamberi B., Dalla-Favera R., Kraemer P. SEN6, a locus for SV40-mediated immortalization of human cells, maps to 6q26-27. Oncogene. 1997 Jan 23;14(3):313–321. doi: 10.1038/sj.onc.1200842. [DOI] [PubMed] [Google Scholar]
  3. Betz R., Gray S. G., Ekström C., Larsson C., Ekström T. J. Human histone deacetylase 2, HDAC2 (Human RPD3), is localized to 6q21 by radiation hybrid mapping. Genomics. 1998 Sep 1;52(2):245–246. doi: 10.1006/geno.1998.5435. [DOI] [PubMed] [Google Scholar]
  4. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  5. Fults D., Pedone C. A., Thomas G. A., White R. Allelotype of human malignant astrocytoma. Cancer Res. 1990 Sep 15;50(18):5784–5789. [PubMed] [Google Scholar]
  6. Henson J. W., Schnitker B. L., Correa K. M., von Deimling A., Fassbender F., Xu H. J., Benedict W. F., Yandell D. W., Louis D. N. The retinoblastoma gene is involved in malignant progression of astrocytomas. Ann Neurol. 1994 Nov;36(5):714–721. doi: 10.1002/ana.410360505. [DOI] [PubMed] [Google Scholar]
  7. Ichimura K., Schmidt E. E., Goike H. M., Collins V. P. Human glioblastomas with no alterations of the CDKN2A (p16INK4A, MTS1) and CDK4 genes have frequent mutations of the retinoblastoma gene. Oncogene. 1996 Sep 5;13(5):1065–1072. [PubMed] [Google Scholar]
  8. Ichimura K., Schmidt E. E., Miyakawa A., Goike H. M., Collins V. P. Distinct patterns of deletion on 10p and 10q suggest involvement of multiple tumor suppressor genes in the development of astrocytic gliomas of different malignancy grades. Genes Chromosomes Cancer. 1998 May;22(1):9–15. doi: 10.1002/(sici)1098-2264(199805)22:1<9::aid-gcc2>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  9. Ichimura K., Schmidt E. E., Yamaguchi N., James C. D., Collins V. P. A common region of homozygous deletion in malignant human gliomas lies between the IFN alpha/omega gene cluster and the D9S171 locus. Cancer Res. 1994 Jun 15;54(12):3127–3130. [PubMed] [Google Scholar]
  10. Jenkins R. B., Kimmel D. W., Moertel C. A., Schultz C. G., Scheithauer B. W., Kelly P. J., Dewald G. W. A cytogenetic study of 53 human gliomas. Cancer Genet Cytogenet. 1989 Jun;39(2):253–279. doi: 10.1016/0165-4608(89)90192-1. [DOI] [PubMed] [Google Scholar]
  11. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S. I., Puc J., Miliaresis C., Rodgers L., McCombie R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997 Mar 28;275(5308):1943–1947. doi: 10.1126/science.275.5308.1943. [DOI] [PubMed] [Google Scholar]
  12. Liang B. C., Ross D. A., Greenberg H. S., Meltzer P. S., Trent J. M. Evidence of allelic imbalance of chromosome 6 in human astrocytomas. Neurology. 1994 Mar;44(3 Pt 1):533–536. doi: 10.1212/wnl.44.3_part_1.533. [DOI] [PubMed] [Google Scholar]
  13. Liu L., Ichimura K., Pettersson E. H., Collins V. P. Chromosome 7 rearrangements in glioblastomas; loci adjacent to EGFR are independently amplified. J Neuropathol Exp Neurol. 1998 Dec;57(12):1138–1145. doi: 10.1097/00005072-199812000-00005. [DOI] [PubMed] [Google Scholar]
  14. Mertens F., Johansson B., Höglund M., Mitelman F. Chromosomal imbalance maps of malignant solid tumors: a cytogenetic survey of 3185 neoplasms. Cancer Res. 1997 Jul 1;57(13):2765–2780. [PubMed] [Google Scholar]
  15. Mohapatra G., Kim D. H., Feuerstein B. G. Detection of multiple gains and losses of genetic material in ten glioma cell lines by comparative genomic hybridization. Genes Chromosomes Cancer. 1995 Jun;13(2):86–93. doi: 10.1002/gcc.2870130203. [DOI] [PubMed] [Google Scholar]
  16. Ponglikitmongkol M., Green S., Chambon P. Genomic organization of the human oestrogen receptor gene. EMBO J. 1988 Nov;7(11):3385–3388. doi: 10.1002/j.1460-2075.1988.tb03211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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. Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo-astrocytomas. Genes Chromosomes Cancer. 1992 Nov;5(4):357–374. doi: 10.1002/gcc.2870050412. [DOI] [PubMed] [Google Scholar]
  18. Rasheed B. K., McLendon R. E., Herndon J. E., Friedman H. S., Friedman A. H., Bigner D. D., Bigner S. H. Alterations of the TP53 gene in human gliomas. Cancer Res. 1994 Mar 1;54(5):1324–1330. [PubMed] [Google Scholar]
  19. Saitoh Y., Bruner J. M., Levin V. A., Kyritsis A. P. Identification of allelic loss on chromosome arm 6p in human astrocytomas by arbitrarily primed polymerase chain reaction. Genes Chromosomes Cancer. 1998 Jul;22(3):165–170. doi: 10.1002/(sici)1098-2264(199807)22:3<165::aid-gcc1>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  20. Sandhu A. K., Kaur G. P., Reddy D. E., Rane N. S., Athwal R. S. A gene on 6q 14-21 restores senescence to immortal ovarian tumor cells. Oncogene. 1996 Jan 18;12(2):247–252. [PubMed] [Google Scholar]
  21. Schmidt E. E., Ichimura K., Goike H. M., Moshref A., Liu L., Collins V. P. Mutational profile of the PTEN gene in primary human astrocytic tumors and cultivated xenografts. J Neuropathol Exp Neurol. 1999 Nov;58(11):1170–1183. doi: 10.1097/00005072-199911000-00007. [DOI] [PubMed] [Google Scholar]
  22. Schmidt E. E., Ichimura K., Messerle K. R., Goike H. M., Collins V. P. Infrequent methylation of CDKN2A(MTS1/p16) and rare mutation of both CDKN2A and CDKN2B(MTS2/p15) in primary astrocytic tumours. Br J Cancer. 1997;75(1):2–8. doi: 10.1038/bjc.1997.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schmidt E. E., Ichimura K., Reifenberger G., Collins V. P. CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. Cancer Res. 1994 Dec 15;54(24):6321–6324. [PubMed] [Google Scholar]
  24. Teyssier J. R., Ferre D. Identification of a clustering of chromosomal breakpoints in the analysis of 203 human primary solid tumor non specific karyotypic rearrangements. Anticancer Res. 1992 May-Jun;12(3):997–1004. [PubMed] [Google Scholar]
  25. Thiel G., Losanowa T., Kintzel D., Nisch G., Martin H., Vorpahl K., Witkowski R. Karyotypes in 90 human gliomas. Cancer Genet Cytogenet. 1992 Feb;58(2):109–120. doi: 10.1016/0165-4608(92)90095-p. [DOI] [PubMed] [Google Scholar]
  26. Trent J. M., Stanbridge E. J., McBride H. L., Meese E. U., Casey G., Araujo D. E., Witkowski C. M., Nagle R. B. Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6. Science. 1990 Feb 2;247(4942):568–571. doi: 10.1126/science.2300817. [DOI] [PubMed] [Google Scholar]
  27. Weber R. G., Sommer C., Albert F. K., Kiessling M., Cremer T. Clinically distinct subgroups of glioblastoma multiforme studied by comparative genomic hybridization. Lab Invest. 1996 Jan;74(1):108–119. [PubMed] [Google Scholar]
  28. Welch D. R., Chen P., Miele M. E., McGary C. T., Bower J. M., Stanbridge E. J., Weissman B. E. Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity. Oncogene. 1994 Jan;9(1):255–262. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES