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Are aberrant transcripts of FHIT, TSG101, and PTEN/MMAC1 oncogenesis related?
1Division of Molecular Medicine, Department of Medical Research, China Medical College Hospital, Taichung, Taiwan, R.O.C.
Abstract:
Tumor suppressor gene mutations in TSG101, FHIT, and PTEN/MMAC1 were found in many types of cancer and the defects in these genes are responsible for the tumor development. Since aberrant transcripts of these genes were also identified in normal tissues, the significance of these mutations in carcinogenesis has become a controversy. To determine large deletions or other alterations in these genes, we analyzed the integrity of their transcripts in both cancerous tissues and the matched normal tissues. More than 400 transcripts derived from at least eight different types of tissue were analyzed using nested RT-PCR and direct sequencing. High frequency of abnormal transcripts of all three genes occurred in both cancerous and the normal tissues. We believe that these aberrant transcripts do not relate to cancer development. These aberrant transcripts may be imperfect products of splicesome that occurs rarely but was amplified by nested RT-PCR. They may be also generated from alternative splicing due to the exonic splicing elements of the gene.
Insights
Aberrant transcripts in tumor suppressor genes like TSG101 and FHIT are common in both cancer and normal tissues, suggesting they do not drive tumor development. These findings challenge the role of such genetic defects in carcinogenesis.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Mutations in tumor suppressor genes (TSG101, FHIT, PTEN/MMAC1) are implicated in various cancers.
- The presence of aberrant transcripts in normal tissues creates controversy regarding their role in carcinogenesis.
Purpose of the Study:
- To investigate the integrity of transcripts for TSG101, FHIT, and PTEN/MMAC1.
- To determine if transcript abnormalities correlate with cancer development by analyzing cancerous and normal tissues.
Main Methods:
- Analysis of over 400 transcripts from at least eight tissue types.
- Utilized nested reverse transcription-polymerase chain reaction (RT-PCR) and direct sequencing.
Main Results:
- High frequencies of abnormal transcripts for all three genes were detected in both cancerous and matched normal tissues.
- The study found no direct correlation between these aberrant transcripts and cancer development.
Conclusions:
- Aberrant transcripts of TSG101, FHIT, and PTEN/MMAC1 are likely not causative factors in tumor initiation.
- These abnormalities may result from rare, amplified spliceosome imperfections or alternative splicing mechanisms.