The DCC gene: Structural analysis and mutations in colorectal carcinomas

Journal Article · Tue Feb 01 00:00:00 EST 1994 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1994.1102· OSTI ID:6553598

Cho, K R; Oliner, J D; Simons, J W; Hedrick, L; Preisinger, A C; Vogelstein, B ^[1]; Fearon, E R ^[2]; Hedge, P ^[3]; Silverman, G A ^[4]

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1. John Hopkins School of Medicine, Baltimore, MD (United States)
2. Yale Univ. School of Medicine, New Haven, CT (United States)
3. Zeneca Pharmaceuticals, Macclesfield (United Kingdom)
4. Harvard Medical School, Boston, MA (United States)

DCC is a candidate tumor-suppressor gene encoding a protein with sequence similarity to cell adhesion molecules such as N-CAM. A set of overlapping YAC clones that contains the entire DCC coding region was isolated. Studies of this YAC contig showed that the DCC gene spans approximately 1.4 Mb. For elucidation of exon-intron structure, lambda phage clones containing all known coding sequences were isolated from a genomic library. These clones were used to demonstrate the existence of 29 DCC exons, and the sequences of the exon-intron boundaries were determined for each. Twenty-three polymorphic markers from chromosome 18 were then studied in a panel of primary colorectal tumors that had lost some, but not all, of chromosome 18. In most of these tumors, the region that was lost included DCC. Finally, Southern blot and PCR-based approaches were used to search for subtle mutations in several DCC exons. One tumor that had a point mutation in exon 28 was found, resulting in a proline to histidine substitution. A second tumor with a point mutation in intron 13 was also found. The regional map and genomic structure of DCC should provide the means to more extensively study DCC gene alterations and protein function in normal and neoplastic cells. 23 refs., 4 figs., 1 tab.

• OSTI ID: 6553598
• Journal Information: Genomics; (United States), Vol. 19:3; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARCINOMAS
PATHOGENESIS
GENE MUTATIONS
DETECTION
HUMAN CHROMOSOME 18
GENETIC MAPPING
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
LARGE INTESTINE
POLYMERASE CHAIN REACTION
RECTUM
BIOTECHNOLOGY
BODY
CHROMOSOMES
CLONING
DIGESTIVE SYSTEM
DISEASES
GASTROINTESTINAL TRACT
GENE AMPLIFICATION
GENETIC ENGINEERING
HUMAN CHROMOSOMES
HYBRIDIZATION
INTESTINES
MAPPING
MUTATIONS
NEOPLASMS
NUCLEIC ACID HYBRIDIZATION
ORGANS
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics