Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors: Correlation with patient age and survival

K. Tada, S. Shiraishi, T. Kamiryo, H. Nakamura, H. Hirano, J. I. Kuratsu, M. Kochi, Hideyuki Saya, Y. Ushio

Research output: Contribution to journalArticle

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Abstract

Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMS. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalJournal of Neurosurgery
Volume95
Issue number4
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 10
Loss of Heterozygosity
Survival
Neoplasms
Astrocytoma
Glioblastoma
Glioma
Genes
Karnofsky Performance Status
Proportional Hazards Models
Microsatellite Repeats

Keywords

  • Age
  • Chromosome 10
  • Glioma
  • Loss of heterozygosity
  • Survival

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Tada, K., Shiraishi, S., Kamiryo, T., Nakamura, H., Hirano, H., Kuratsu, J. I., ... Ushio, Y. (2001). Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors: Correlation with patient age and survival. Journal of Neurosurgery, 95(4), 651-659.

Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors : Correlation with patient age and survival. / Tada, K.; Shiraishi, S.; Kamiryo, T.; Nakamura, H.; Hirano, H.; Kuratsu, J. I.; Kochi, M.; Saya, Hideyuki; Ushio, Y.

In: Journal of Neurosurgery, Vol. 95, No. 4, 2001, p. 651-659.

Research output: Contribution to journalArticle

Tada, K, Shiraishi, S, Kamiryo, T, Nakamura, H, Hirano, H, Kuratsu, JI, Kochi, M, Saya, H & Ushio, Y 2001, 'Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors: Correlation with patient age and survival', Journal of Neurosurgery, vol. 95, no. 4, pp. 651-659.
Tada, K. ; Shiraishi, S. ; Kamiryo, T. ; Nakamura, H. ; Hirano, H. ; Kuratsu, J. I. ; Kochi, M. ; Saya, Hideyuki ; Ushio, Y. / Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors : Correlation with patient age and survival. In: Journal of Neurosurgery. 2001 ; Vol. 95, No. 4. pp. 651-659.
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abstract = "Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32{\%}) of 34 AAs and 34 (56{\%}) of 61 GBMS. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41{\%} of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37{\%}) had supratentorial AAs and 56 (63{\%}) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.",
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T1 - Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors

T2 - Correlation with patient age and survival

AU - Tada, K.

AU - Shiraishi, S.

AU - Kamiryo, T.

AU - Nakamura, H.

AU - Hirano, H.

AU - Kuratsu, J. I.

AU - Kochi, M.

AU - Saya, Hideyuki

AU - Ushio, Y.

PY - 2001

Y1 - 2001

N2 - Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMS. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

AB - Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMS. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

KW - Age

KW - Chromosome 10

KW - Glioma

KW - Loss of heterozygosity

KW - Survival

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C2 - 11596960

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