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Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in cervical cancer
1Division of Molecular Medicine, China Medical College Hospital, Taichung, Taiwan.
Objective:
PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be homozygously deleted or mutated in several different types of human tumors. The aim of this study is to determine whether PTEN/MMAC1 is a target for 10q loss of heterozygosity in cervical cancer.
Method:
We examined 50 primary cervical carcinoma specimens using a PCR-based assay followed by SSCP and direct sequencing. The genomic DNA was also confirmed by Southern blot analysis.
Results:
All specimens except one, which has a 7-base deletion, showed a negative result. Among them, 30 randomly selected cases and their paired noncancerous tissue were further screened using nested RT-PCR. Six of 30 cervical cancerous tissues had aberrant transcripts. However, 4 of the matched noncancerous tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA did not reveal any evidence of gene alteration.
Conclusions:
Sequence abnormalities in the PTEN/MMAC1 gene were only detected in 1 of 50 cervical cancers analyzed indicating that aberrant PTEN/MMAC1 function is an uncommon event in the development of cervix cancers. However, similar to studies with the TSG101 gene, screening for aberrant transcripts of PTEN/MMAC1 with nested RT-PCR may detect transcripts, which, although they vary from the normal size, may not be related to oncogenesis as they are also frequently found in normal tissues of the same patient.
Insights
Mutations in the PTEN/MMAC1 gene are uncommon in cervical cancer development. Aberrant transcripts detected via nested RT-PCR in cervical tumors were also found in normal tissues, suggesting they are not oncogenic drivers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- PTEN/MMAC1 is a candidate tumor suppressor gene at chromosome 10q23.3.
- This gene is frequently deleted or mutated in various human tumors.
Purpose of the Study:
- To investigate if PTEN/MMAC1 is a target of 10q loss of heterozygosity in cervical cancer.
- To analyze PTEN/MMAC1 alterations in cervical carcinoma specimens.
Main Methods:
- Examined 50 primary cervical carcinoma specimens using PCR-based assay, SSCP, and direct sequencing.
- Confirmed genomic DNA integrity with Southern blot analysis.
- Screened 30 cases and paired noncancerous tissues for aberrant transcripts using nested RT-PCR.
Main Results:
- Only one of 50 cervical cancers showed a 7-base deletion in PTEN/MMAC1.
- Aberrant PTEN/MMAC1 transcripts were found in 6 of 30 cancerous tissues.
- Notably, 4 of the matched noncancerous tissues also exhibited aberrant transcripts.
- Southern blot analysis revealed no genomic alterations in PTEN/MMAC1.
Conclusions:
- Sequence abnormalities in PTEN/MMAC1 are rare in cervical cancer development.
- Aberrant transcripts detected by nested RT-PCR in tumors may not be oncogenic, as they frequently occur in normal tissues.
- PTEN/MMAC1 alterations are an uncommon event in cervical carcinogenesis.