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PTEN/MMAC1 mutations and EGFR amplification in glioblastomas
W Liu1, C D James, L Frederick
1Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Cancer Research
|December 11, 1997
Summary
Loss of heterozygosity (LOH) on chromosome 10 is common in glioblastoma. PTEN/MMAC1 gene alterations were found in 27% of tumors, often with LOH, indicating its role as a tumor suppressor.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Glioblastoma (grade IV glioma) frequently exhibits loss of heterozygosity (LOH) on chromosome 10.
- PTEN/MMAC1 is a candidate tumor suppressor gene potentially affected by chromosome 10 LOH.
Purpose of the Study:
- To investigate PTEN/MMAC1 gene alterations in glioblastoma.
- To determine the frequency of PTEN/MMAC1 mutations and deletions.
- To assess the relationship between PTEN/MMAC1 status and EGFR amplification.
Main Methods:
- Analysis of 63 glioblastoma samples for PTEN/MMAC1 alterations.
- Microsatellite analysis of normal-tumor DNA pairs to detect LOH.
- Competitive PCR assays to identify homozygous deletions of PTEN/MMAC1.
- Assessment of EGFR amplification frequency.
Main Results:
- PTEN/MMAC1 sequence changes affecting the protein were identified in 17 (27%) of 63 glioblastomas.
- LOH near PTEN/MMAC1 was observed in 13 of 14 informative cases, suggesting deletion of the remaining allele.
- Three glioblastoma samples showed homozygous deletions of PTEN/MMAC1.
- EGFR amplification occurred similarly in tumors with or without PTEN/MMAC1 alterations.
Conclusions:
- PTEN/MMAC1 inactivation is a frequent event in glioblastoma, often involving LOH and/or homozygous deletion.
- EGFR amplification and PTEN/MMAC1 inactivation may represent parallel pathways in glioblastoma development.
- EGFR signaling-driven growth may not strictly depend on PTEN/MMAC1 inactivation.