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DCC expression is altered by multiple mechanisms in brain tumours
B C Ekstrand1, T A Mansfield, S H Bigner
1Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Abstract:
The DCC (deleted in colorectal cancer) candidate tumor suppressor gene spans greater than 1350 kilobases at chromosomes 18q21.1 and encodes a transmembrane protein of unknown function. Although DCC is expressed in a number of adult tissues, its expression is highest in the brain and we have, therefore, undertaken studies to determine if DCC inactivation might contribute to tumors arising there. Decreased or absent DCC protein expression was noted in more than 50% of the thirty brain tumors studied. Although specific mutations in the DCC gene were not identified, a variety of mechanisms appeared to contribute to the altered DCC expression, including allelic loss, aberrant splicing of transcripts and allele-specific loss of transcripts. In total, the data suggest that DCC inactivation may be important in brain tumor pathogenesis.
Insights
The deleted in colorectal cancer (DCC) gene, crucial for brain tumor development, showed decreased or absent protein expression in over half of brain tumors studied. Its inactivation may play a significant role in brain tumor formation.
Area of Science:
- Oncology
- Genetics
- Neuroscience
Background:
- The deleted in colorectal cancer (DCC) gene is a large candidate tumor suppressor gene located at chromosome 18q21.1.
- DCC encodes a transmembrane protein with a currently unknown function.
- DCC exhibits high expression levels in the brain compared to other adult tissues.
Purpose of the Study:
- To investigate the potential role of DCC inactivation in the pathogenesis of brain tumors.
- To determine if alterations in DCC expression are present in brain tumor samples.
Main Methods:
- Analysis of DCC protein expression in a cohort of thirty brain tumors.
- Investigation of potential mechanisms for altered DCC expression, including allelic loss, aberrant splicing, and allele-specific transcript loss.
Main Results:
- Over 50% of the studied brain tumors displayed decreased or absent DCC protein expression.
- Specific mutations within the DCC gene were not identified in the analyzed tumors.
- Altered DCC expression was attributed to various mechanisms such as allelic loss and aberrant splicing.
Conclusions:
- DCC inactivation, through mechanisms other than direct mutation, appears to be a significant factor in brain tumor development.
- The findings suggest DCC is a relevant tumor suppressor in the context of brain oncogenesis.