Abstract
p16 is involved in a cell cycle regulatory cascade that includes cyclin- dependent kinase 4 (cdk4), cyclin DI and pRb. Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or GBM cell lines, and alterations of the individual components of this pathway appear inversely correlated with one another. While this suggests that disruption of any individual component has similar oncogenic effects, homozygous deletions of the CDKN2/p16 gene are the most common genetic alteration. We investigated the relationship between homozygous CDKN2/p16 deletions and cellular proliferation in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma. 15 grade II astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a comparative multiplex PCR assay, homozygous deletions of the CDKN2/p16 gene were detected in 5 anaplastic astrocytomas (25% and 6 GBMs (46%), but in none of the lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of proliferating cells in the same samples used for molecular genetic analysis. In both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were significantly higher in tumors with CDKN2/p16 deletions (20%t than in those without deletions (1()%; p=0.000l). These results suggest that homozygous CDKN2/p16 deletions in high grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p16-cdk4- cyclin D1-pRb pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions are more common genetic events in high-grade astrocytomas than RB mutations or CDK4 amplification.
| Original language | English |
|---|---|
| Pages (from-to) | 1026-1031 |
| Number of pages | 6 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 55 |
| Issue number | 10 |
| Publication status | Published - Oct 1996 |
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Keywords
- Astrocytoma
- CDKN2
- Cell cycle
- Ki-67
- p16
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neuroscience(all)
Cite this
Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices. / Ono, Yasuhiro; Tamiya, Takashi; Ichikawa, Tomotsugu; Kunishio, Katsuzou; Matsumoto, Kengo; Furuta, Tomohisa; Ohmoto, Takashi; Ueki, Keisuke; Louis, David N.
In: Journal of Neuropathology and Experimental Neurology, Vol. 55, No. 10, 10.1996, p. 1026-1031.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices
AU - Ono, Yasuhiro
AU - Tamiya, Takashi
AU - Ichikawa, Tomotsugu
AU - Kunishio, Katsuzou
AU - Matsumoto, Kengo
AU - Furuta, Tomohisa
AU - Ohmoto, Takashi
AU - Ueki, Keisuke
AU - Louis, David N.
PY - 1996/10
Y1 - 1996/10
N2 - p16 is involved in a cell cycle regulatory cascade that includes cyclin- dependent kinase 4 (cdk4), cyclin DI and pRb. Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or GBM cell lines, and alterations of the individual components of this pathway appear inversely correlated with one another. While this suggests that disruption of any individual component has similar oncogenic effects, homozygous deletions of the CDKN2/p16 gene are the most common genetic alteration. We investigated the relationship between homozygous CDKN2/p16 deletions and cellular proliferation in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma. 15 grade II astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a comparative multiplex PCR assay, homozygous deletions of the CDKN2/p16 gene were detected in 5 anaplastic astrocytomas (25% and 6 GBMs (46%), but in none of the lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of proliferating cells in the same samples used for molecular genetic analysis. In both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were significantly higher in tumors with CDKN2/p16 deletions (20%t than in those without deletions (1()%; p=0.000l). These results suggest that homozygous CDKN2/p16 deletions in high grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p16-cdk4- cyclin D1-pRb pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions are more common genetic events in high-grade astrocytomas than RB mutations or CDK4 amplification.
AB - p16 is involved in a cell cycle regulatory cascade that includes cyclin- dependent kinase 4 (cdk4), cyclin DI and pRb. Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or GBM cell lines, and alterations of the individual components of this pathway appear inversely correlated with one another. While this suggests that disruption of any individual component has similar oncogenic effects, homozygous deletions of the CDKN2/p16 gene are the most common genetic alteration. We investigated the relationship between homozygous CDKN2/p16 deletions and cellular proliferation in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma. 15 grade II astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a comparative multiplex PCR assay, homozygous deletions of the CDKN2/p16 gene were detected in 5 anaplastic astrocytomas (25% and 6 GBMs (46%), but in none of the lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of proliferating cells in the same samples used for molecular genetic analysis. In both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were significantly higher in tumors with CDKN2/p16 deletions (20%t than in those without deletions (1()%; p=0.000l). These results suggest that homozygous CDKN2/p16 deletions in high grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p16-cdk4- cyclin D1-pRb pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions are more common genetic events in high-grade astrocytomas than RB mutations or CDK4 amplification.
KW - Astrocytoma
KW - CDKN2
KW - Cell cycle
KW - Ki-67
KW - p16
UR - http://www.scopus.com/inward/record.url?scp=0029823960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029823960&partnerID=8YFLogxK
M3 - Article
C2 - 8857999
AN - SCOPUS:0029823960
VL - 55
SP - 1026
EP - 1031
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 10
ER -