Related Experiment Videos
Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers
T Kohno1, M Takahashi, R Manda
1Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
The PTEN/MMAC1/TEP1 gene has been isolated as a tumor suppressor gene that is altered in several types of human tumors including brain, breast, and prostate cancers. In the present study, we report PTEN/MMAC1/TEP1 alterations in human lung cancers. Intragenic homozygous deletions were detected in 6 (40%) of 15 small cell lung carcinoma (SCLC) cell lines and in 2 (8%) of 25 non-small cell lung carcinoma (NSCLC) cell lines. A nonsense mutation and a missense mutation were detected in 2 (8%) NSCLC cell lines. An intragenic homozygous deletion, a 1-bp frameshift mutation, and a nonsense somatic mutation were also detected in three (6%) of 47 surgical specimens. All the lung tumors with PTEN/MMAC1/TEP1 mutations were homozygous for the mutant alleles. These findings suggest that PTEN/MMAC1/TEP1 plays a role as a tumor suppressor gene in the genesis and/or progression of human lung cancer.
Insights
The PTEN/MMAC1/TEP1 gene, a tumor suppressor, shows alterations in human lung cancers. Homozygous deletions and mutations were found in small cell lung carcinoma and non-small cell lung carcinoma, indicating its role in lung cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The PTEN/MMAC1/TEP1 gene is recognized as a tumor suppressor involved in various human cancers.
- Alterations in this gene have been observed in brain, breast, and prostate tumors.
Purpose of the Study:
- To investigate the presence and nature of PTEN/MMAC1/TEP1 alterations in human lung cancers.
- To determine the role of PTEN/MMAC1/TEP1 in the development and progression of lung cancer.
Main Methods:
- Analysis of PTEN/MMAC1/TEP1 in 15 small cell lung carcinoma (SCLC) cell lines and 25 non-small cell lung carcinoma (NSCLC) cell lines.
- Detection of intragenic homozygous deletions, point mutations (nonsense, missense), and frameshift mutations in SCLC and NSCLC cell lines and 47 surgical specimens.
- Genotyping of lung tumors to identify homozygous mutant alleles.
Main Results:
- Homozygous deletions of PTEN/MMAC1/TEP1 were found in 40% of SCLC cell lines and 8% of NSCLC cell lines.
- Mutations including nonsense, missense, frameshift, and homozygous deletions were identified in NSCLC cell lines and surgical specimens.
- All analyzed lung tumors with PTEN/MMAC1/TEP1 mutations were homozygous for the mutant alleles.
Conclusions:
- PTEN/MMAC1/TEP1 alterations are present in human lung cancers, including SCLC and NSCLC.
- The homozygous nature of these mutations suggests a significant role for PTEN/MMAC1/TEP1 as a tumor suppressor in lung carcinogenesis.
- These findings highlight PTEN/MMAC1/TEP1's involvement in the genesis and/or progression of lung cancer.