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The DCC gene: structural analysis and mutations in colorectal carcinomas
K R Cho1, J D Oliner, J W Simons
1Johns Hopkins Oncology Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
Genomics
|February 1, 1994
Summary
The Deleted in Colorectal Carcinoma (DCC) gene, a tumor suppressor, spans 1.4 Mb and has 29 exons. Researchers identified subtle mutations in DCC in colorectal tumors, aiding future studies of its function.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- The Deleted in Colorectal Carcinoma (DCC) gene is a candidate tumor suppressor.
- DCC encodes a protein similar to cell adhesion molecules like N-CAM.
- Understanding DCC's genomic structure is crucial for studying its role in cancer.
Purpose of the Study:
- To isolate and characterize the genomic structure of the DCC gene.
- To determine the exon-intron organization of DCC.
- To investigate DCC alterations in colorectal tumors.
Main Methods:
- Isolation of Yeast Artificial Chromosome (YAC) clones to map the DCC gene.
- Characterization of lambda phage clones to define DCC's exon-intron structure.
- Analysis of colorectal tumors using polymorphic markers, Southern blots, and PCR to detect mutations.
Main Results:
- The DCC gene spans approximately 1.4 Mb and comprises 29 exons.
- Loss of the chromosomal region containing DCC was observed in most studied colorectal tumors.
- Subtle mutations, including a missense mutation in exon 28 and an intronic mutation in intron 13, were identified in two tumors.
Conclusions:
- The established genomic map and structure of DCC facilitate further investigation into gene alterations.
- This research provides a foundation for studying DCC's function in both normal and neoplastic cells.
- Detailed knowledge of DCC's genomic organization is essential for understanding its tumor-suppressive mechanisms.