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Identification and mutation analysis of DOC-1R, a DOC-1 growth suppressor-related gene
1Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Abstract:
The tumor suppressor gene MEN1 and several oncogenes including CCND1/cyclin D1/PRAD1 map to chromosome 11q13. However, molecular and cytogenetic analysis suggests the presence of a second tumor suppressor locus at this chromosome region. We have identified a novel gene from chromosome 11q13, which encodes a protein of 126 amino acids sharing an overall 57% identity with the p12(DOC-1) protein encoded by the DOC-1 gene, the human homolog of hamster putative tumor suppressor doc-1 (deleted in oral cancer-1). We therefore designated the novel gene as DOC-1R for DOC-1-related. The cytogenetic location was confirmed by chromosome fluorescent in situ hybridization. Northern blot analysis indicated that it was expressed in all the tissues examined. DOC-1R protein showed heterogeneous subcellular localization. RT-PCR-SSCP analysis failed to detect deleterious mutations of the DOC-1R transcript in four premalignant oral keratinocyte lines and 20 different cancer cell lines from tumor types which frequently harbor LOH at chromosome 11q13.
Insights
Researchers identified a novel gene, DOC-1R, on chromosome 11q13. This gene, related to the deleted in oral cancer-1 (DOC-1) tumor suppressor, shows expression in various tissues but lacks mutations in oral cancer cell lines.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Chromosome 11q13 is implicated in tumorigenesis, housing tumor suppressor genes like MEN1 and oncogenes such as CCND1.
- Previous analyses suggested a potential second tumor suppressor locus within the 11q13 region.
- The deleted in oral cancer-1 (DOC-1) gene is a putative tumor suppressor linked to oral cancer.
Purpose of the Study:
- To identify and characterize a novel gene located at chromosome 11q13.
- To investigate the relationship of this novel gene to known tumor suppressor genes in the 11q13 region.
- To assess the mutational status of the novel gene in premalignant and cancerous cell lines.
Main Methods:
- Gene identification and sequencing.
- Protein homology analysis.
- Cytogenetic localization using fluorescent in situ hybridization (FISH).
- Gene expression analysis via Northern blotting.
- Subcellular localization studies.
- Mutation screening using RT-PCR-SSCP analysis.
Main Results:
- A novel gene, designated DOC-1R (DOC-1-related), was identified on chromosome 11q13.
- DOC-1R encodes a 126-amino acid protein with 57% identity to the p12(DOC-1) protein.
- FISH confirmed the cytogenetic location of DOC-1R.
- Northern blot analysis revealed ubiquitous expression of DOC-1R across examined tissues.
- DOC-1R protein exhibited heterogeneous subcellular localization.
- RT-PCR-SSCP analysis detected no deleterious mutations in DOC-1R transcripts from oral keratinocyte lines or various cancer cell lines.
Conclusions:
- DOC-1R is a newly identified gene on chromosome 11q13 with homology to the DOC-1 tumor suppressor.
- Its widespread expression and lack of detectable mutations in specific cancer cell lines suggest a complex role in tumorigenesis.
- Further research is needed to elucidate the precise function and involvement of DOC-1R in cancer development.