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Alterations of the tumour suppressor gene DCC in neuroblastoma
Abstract:
The deleted in colorectal carcinoma (DCC) gene, a candidate tumour suppressor, might be inactivated in a number of human cancers. In order to evaluate the possible role of DCC alterations in the pathogenesis of neuroblastoma, we examined 25 neuroblastoma cell lines and 16 primary tumours, including 6 samples with loss of heterozygosity (LOH) at the DCC locus for DCC mRNA expression, by using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. The level of DCC expression was significantly reduced or undetectable in 12 of 25 (48%) cell lines and 7 of 16 (44%) primary tumours, suggesting that inactivation of the DCC gene is involved in the development of neuroblastoma. Three of the 6 tumours with LOH at the DCC locus revealed reduced DCC mRNA expression, indicating that LOH at the DCC locus might have affected the levels of DCC mRNA. We also screened for mutations in 4 exons of the DCC gene in 12 cell lines by using PCR-single strand conformation polymorphism (PCR-SSCP) analysis. Point mutations were not found except a polymorphic change at codon 201. The mechanism for inactivation of the DCC gene will be further investigated.
Insights
The deleted in colorectal carcinoma (DCC) gene shows reduced expression in nearly half of neuroblastoma cell lines and tumors. This suggests DCC gene inactivation plays a role in neuroblastoma development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The deleted in colorectal carcinoma (DCC) gene is a potential tumor suppressor implicated in various human cancers.
- Understanding DCC gene alterations is crucial for investigating neuroblastoma pathogenesis.
Purpose of the Study:
- To evaluate the role of DCC gene alterations in the development of neuroblastoma.
- To assess DCC mRNA expression levels in neuroblastoma cell lines and primary tumors.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze DCC mRNA expression.
- Loss of heterozygosity (LOH) at the DCC locus was examined in primary tumors.
- PCR-single strand conformation polymorphism (PCR-SSCP) analysis screened for mutations in DCC gene exons.
Main Results:
- Significantly reduced or undetectable DCC mRNA expression was observed in 48% of cell lines and 44% of primary tumors.
- Three out of six tumors with LOH at the DCC locus showed decreased DCC mRNA expression.
- No point mutations were detected in the screened DCC gene exons, apart from a polymorphic change.
Conclusions:
- DCC gene inactivation is implicated in the development of neuroblastoma.
- LOH at the DCC locus may contribute to reduced DCC mRNA levels.
- Further investigation is needed to elucidate the precise mechanisms of DCC gene inactivation in neuroblastoma.