Related Experiment Videos
Infrequent mutations in the PTEN/MMAC1 gene among primary breast cancers
1Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita.
Abstract:
Recently PTEN/MMAC1, a candidate tumor suppressor gene, was isolated from chromosome 10q23-24 and somatic mutations of this gene were detected in several malignancies including brain, prostate, and breast tumors. To investigate further the potential role of this gene in mammary carcinogenesis, we examined 69 primary breast cancers for mutations in PTEN/MMAC1 by means of polymerase chain reaction single-strand conformation polymorphism and sequencing analysis. We detected only one somatic missense mutation, a change from T to C at codon 59 (TCA to CCA) resulting in substitution of Pro for Ser in the predicted protein. This site is located outside of phosphatase or phosphate-acceptor motifs, but this codon encodes a residue that is conserved in homologous proteins, tensin and auxilin and is likely to be crucial for normal function of PTEN/MMAC1. Among the 69 tumors examined, three low-frequency polymorphisms were found as well, one in the non-coding region of exon 1 and one each in introns 2 and 7. Our results suggested that mutation of the PTEN/MMAC1 gene is not a major factor in the development of most primary breast cancers.
Insights
Mutations in the PTEN/MMAC1 tumor suppressor gene are uncommon in primary breast cancers. This study found only one somatic mutation in 69 tumors, suggesting PTEN/MMAC1 is not a major factor in breast cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The PTEN/MMAC1 gene, a candidate tumor suppressor, is located on chromosome 10q23-24.
- Somatic mutations in PTEN/MMAC1 have been identified in various cancers, including brain, prostate, and breast tumors.
- Its role in mammary carcinogenesis warrants further investigation.
Purpose of the Study:
- To investigate the potential role of the PTEN/MMAC1 gene in breast cancer development.
- To screen primary breast cancers for mutations in the PTEN/MMAC1 gene.
Main Methods:
- Analysis of 69 primary breast cancer samples.
- Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and sequencing for mutation detection.
Main Results:
- Only one somatic missense mutation (codon 59, Ser to Pro) was detected in the PTEN/MMAC1 gene among 69 primary breast cancers.
- This mutation occurred outside known functional motifs but in a conserved residue.
- Three low-frequency polymorphisms were identified in non-coding and intronic regions.
Conclusions:
- PTEN/MMAC1 gene mutation is not a significant factor in the pathogenesis of most primary breast cancers.
- The low mutation rate suggests limited involvement of PTEN/MMAC1 in mammary carcinogenesis.
- Further research may explore the function of the identified mutation and polymorphisms.