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MTS1/p16/CDKN2 lesions in primary glioblastoma multiforme
T Moulton1, G Samara, W Y Chung
1Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York.
The American Journal of Pathology
|March 1, 1995
Summary
The multiple tumor suppressor 1 (MTS1) gene, crucial for regulating cell division, is frequently deleted or mutated in glioblastoma multiforme (GBM). These genetic alterations in MTS1/p16/CDKN2 support its role as a tumor suppressor in GBM development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The multiple tumor suppressor 1 (MTS1) gene, encoding p16, is a known tumor suppressor frequently altered in various cancers.
- MTS1/p16/CDKN2 and the related MTS2/p15 genes are located on chromosome 9p21, a region often deleted in malignant gliomas.
Purpose of the Study:
- To investigate the frequency and nature of genetic lesions in MTS1/p16/CDKN2 and MTS2/p15 in primary glioblastoma multiforme (GBM) biopsies.
- To determine the role of MTS1/p16/CDKN2 as a tumor suppressor gene in the in vivo progression of GBM.
Main Methods:
- Analysis of primary GBM biopsies for homozygous deletions and intragenic mutations in MTS1/p16/CDKN2 and MTS2/p15.
- Comparison of genetic alterations between high-grade GBM and low-grade gliomas.
- Investigation of DNA deletion breakpoints between the two genes.
Main Results:
- Homozygous deletion of MTS1/p16/CDKN2 was observed in 9 out of 27 GBM cases.
- A low frequency of intragenic MTS1/p16/CDKN2 mutations, including a premature termination mutation, was detected.
- No mutations were found in MTS2/p15 exon 2; one GBM showed a deletion between MTS1 and MTS2.
- MTS1/p16/CDKN2 deletions were absent in low-grade gliomas, contrasting with high-grade GBM.
Conclusions:
- The data strongly support a role for MTS1/p16/CDKN2 as a tumor suppressor gene in the development of GBM.
- The findings suggest the potential involvement of additional tumor suppressor genes on chromosome 9p21, as some GBMs with deletions lacked detectable intragenic mutations.