Abstract
Unexpectedly aggressive clinical course of some grade II astrocytomas is a diagnostic dilemma for routine histopathology. Because increasing tumor malignancy is a consequence of progressive accumulation of chromosomal alterations, we investigated whether aggressive behavior of grade II astrocytomas could be predicted by the number and type of gross chromosomal aberrations. We used comparative genomic hybridization to analyze 11 grade II astrocytomas with typical (good, n = 7) or poor (n = 4) prognosis. The results were also compared with a reference material of 13 grade III-IV astrocytomas and nine established cell lines. We found a median of two aberrations (range 0 to 4) in tumors with good prognosis and of 15.5 changes (range 8 to 28) in tumors with poor prognosis. Chromosomal gains were present in both groups, whereas chromosomal losses were frequent in tumors with poor prognosis (median 9.5, range 3 to 14) but rare in tumors with good prognosis (range 0 to 2). All chromosomal gains were also found in the high-grade astrocytoma group and the majority of them in cell lines. Chromosomal losses in grade II astrocytomas with poor prognosis were very similar to those in grade III-IV astrocytomas and cell lines. We conclude that an early accumulation of genetic changes in grade II astrocytomas is closely associated with poor patient prognosis, suggesting diagnostic use for comparative genomic hybridization in characterization of grade II astrocytomas.
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- Haapasalo H., Isola J., Sallinen P., Kalimo H., Helin H., Rantala I. Aberrant p53 expression in astrocytic neoplasms of the brain: association with proliferation. Am J Pathol. 1993 May;142(5):1347–1351. [PMC free article] [PubMed] [Google Scholar]
- Hyytinen E. R., Thalmann G. N., Zhau H. E., Karhu R., Kallioniemi O. P., Chung L. W., Visakorpi T. Genetic changes associated with the acquisition of androgen-independent growth, tumorigenicity and metastatic potential in a prostate cancer model. Br J Cancer. 1997;75(2):190–195. doi: 10.1038/bjc.1997.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isola J. J., Kallioniemi O. P., Chu L. W., Fuqua S. A., Hilsenbeck S. G., Osborne C. K., Waldman F. M. Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. Am J Pathol. 1995 Oct;147(4):905–911. [PMC free article] [PubMed] [Google Scholar]
- Isola J., DeVries S., Chu L., Ghazvini S., Waldman F. Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. Am J Pathol. 1994 Dec;145(6):1301–1308. [PMC free article] [PubMed] [Google Scholar]
- Kallioniemi A., Kallioniemi O. P., Sudar D., Rutovitz D., Gray J. W., Waldman F., Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992 Oct 30;258(5083):818–821. doi: 10.1126/science.1359641. [DOI] [PubMed] [Google Scholar]
- Kallioniemi O. P., Kallioniemi A., Piper J., Isola J., Waldman F. M., Gray J. W., Pinkel D. Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer. 1994 Aug;10(4):231–243. doi: 10.1002/gcc.2870100403. [DOI] [PubMed] [Google Scholar]
- Karhu R., Siitonen S., Tanner M., Keinänen M., Mäkipernaa A., Lehtinen M., Vilpo J. A., Isola J. Genetic aberrations in pediatric acute lymphoblastic leukemia by comparative genomic hybridization. Cancer Genet Cytogenet. 1997 Jun;95(2):123–129. doi: 10.1016/s0165-4608(96)00242-7. [DOI] [PubMed] [Google Scholar]
- Kim D. H., Mohapatra G., Bollen A., Waldman F. M., Feuerstein B. G. Chromosomal abnormalities in glioblastoma multiforme tumors and glioma cell lines detected by comparative genomic hybridization. Int J Cancer. 1995 Mar 16;60(6):812–819. doi: 10.1002/ijc.2910600615. [DOI] [PubMed] [Google Scholar]
- Kuukasjärvi T., Karhu R., Tanner M., Kähkönen M., Schäffer A., Nupponen N., Pennanen S., Kallioniemi A., Kallioniemi O. P., Isola J. Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Res. 1997 Apr 15;57(8):1597–1604. [PubMed] [Google Scholar]
- Kuukasjärvi T., Tanner M., Pennanen S., Karhu R., Kallioniemi O. P., Isola J. Genetic changes in intraductal breast cancer detected by comparative genomic hybridization. Am J Pathol. 1997 Apr;150(4):1465–1471. [PMC free article] [PubMed] [Google Scholar]
- Kuukasjärvi T., Tanner M., Pennanen S., Karhu R., Visakorpi T., Isola J. Optimizing DOP-PCR for universal amplification of small DNA samples in comparative genomic hybridization. Genes Chromosomes Cancer. 1997 Feb;18(2):94–101. [PubMed] [Google Scholar]
- Louis D. N. A molecular genetic model of astrocytoma histopathology. Brain Pathol. 1997 Apr;7(2):755–764. doi: 10.1111/j.1750-3639.1997.tb01062.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Louis D. N., Gusella J. F. A tiger behind many doors: multiple genetic pathways to malignant glioma. Trends Genet. 1995 Oct;11(10):412–415. doi: 10.1016/s0168-9525(00)89125-8. [DOI] [PubMed] [Google Scholar]
- McCormack B. M., Miller D. C., Budzilovich G. N., Voorhees G. J., Ransohoff J. Treatment and survival of low-grade astrocytoma in adults--1977-1988. Neurosurgery. 1992 Oct;31(4):636–642. doi: 10.1227/00006123-199210000-00004. [DOI] [PubMed] [Google Scholar]
- Philippon J. H., Clemenceau S. H., Fauchon F. H., Foncin J. F. Supratentorial low-grade astrocytomas in adults. Neurosurgery. 1993 Apr;32(4):554–559. doi: 10.1227/00006123-199304000-00010. [DOI] [PubMed] [Google Scholar]
- Pollack I. F., Claassen D., al-Shboul Q., Janosky J. E., Deutsch M. Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg. 1995 Apr;82(4):536–547. doi: 10.3171/jns.1995.82.4.0536. [DOI] [PubMed] [Google Scholar]
- Schiffer D., Cavalla P., Chiò A., Richiardi P., Giordana M. T. Proliferative activity and prognosis of low-grade astrocytomas. J Neurooncol. 1997 Aug;34(1):31–35. doi: 10.1023/a:1005755119526. [DOI] [PubMed] [Google Scholar]
- Schlegel J., Scherthan H., Arens N., Stumm G., Kiessling M. Detection of complex genetic alterations in human glioblastoma multiforme using comparative genomic hybridization. J Neuropathol Exp Neurol. 1996 Jan;55(1):81–87. doi: 10.1097/00005072-199601000-00008. [DOI] [PubMed] [Google Scholar]
- Schröck E., Blume C., Meffert M. C., du Manoir S., Bersch W., Kiessling M., Lozanowa T., Thiel G., Witkowski R., Ried T. Recurrent gain of chromosome arm 7q in low-grade astrocytic tumors studied by comparative genomic hybridization. Genes Chromosomes Cancer. 1996 Apr;15(4):199–205. doi: 10.1002/(SICI)1098-2264(199604)15:4<199::AID-GCC1>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
- Schröck E., Thiel G., Lozanova T., du Manoir S., Meffert M. C., Jauch A., Speicher M. R., Nürnberg P., Vogel S., Jänisch W. Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and nonrandom chromosomal gains and losses. Am J Pathol. 1994 Jun;144(6):1203–1218. [PMC free article] [PubMed] [Google Scholar]
- Watanabe K., Tachibana O., Yonekawa Y., Kleihues P., Ohgaki H. Role of gemistocytes in astrocytoma progression. Lab Invest. 1997 Feb;76(2):277–284. [PubMed] [Google Scholar]
- Weber R. G., Sabel M., Reifenberger J., Sommer C., Oberstrass J., Reifenberger G., Kiessling M., Cremer T. Characterization of genomic alterations associated with glioma progression by comparative genomic hybridization. Oncogene. 1996 Sep 5;13(5):983–994. [PubMed] [Google Scholar]
- 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]
- von Deimling A., von Ammon K., Schoenfeld D., Wiestler O. D., Seizinger B. R., Louis D. N. Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol. 1993 Jan;3(1):19–26. doi: 10.1111/j.1750-3639.1993.tb00721.x. [DOI] [PubMed] [Google Scholar]

