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Mutational and LOH Analyses of the Chromosome 4q Region in Esophageal Adenocarcinoma
- Source :
- Oncology. 70:168-172
- Publication Year :
- 2006
- Publisher :
- S. Karger AG, 2006.
-
Abstract
- Objective: Mortality due to esophageal adenocarcinoma has risen markedly, but the molecular mechanisms underlying this carcinogenesis are still incompletely understood. Findings from loss of heterozygosity (LOH) studies have suggested that the long arm of chromosome 4 might harbor tumor suppressor genes relevant to esophageal adenocarcinoma. Methods: We performed LOH analysis of 4q in esophageal adenocarcinomas. Regions of LOH were further evaluated by studying two candidate tumor suppressor genes, hCDC4 and CARF, located within them. Results: 54% of the adenocarcinomas examined showed allelic deletion. LOH was observed in 53, 40, 32, 38, and 27% of tumors at positions D4S1554 (the locus of CARF), D4S1572, D4S1548, D4S2934, and D4S3021, respectively. An area of allelic deletion (spanning 3 million bases) was identified at 4q31.1–3 in 37% of tumors. This region harbors a candidate tumor suppressor gene: hCDC4. However, sequencing of the coding regions of CARF and hCDC4 at 4q35 and 4q31, respectively, did not identify mutations. Conclusions: Our findings demonstrate frequent LOH in esophageal adenocarcinoma at several loci including a novel area of allelic deletion at 4q31.1–3. The results imply that mutational or other alterations at these loci may be involved in the pathogenesis of esophageal adenocarcinoma. Candidate tumor suppressor genes located within these regions merit further study.
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
F-Box-WD Repeat-Containing Protein 7
Esophageal Neoplasms
Tumor suppressor gene
Ubiquitin-Protein Ligases
DNA Mutational Analysis
Loss of Heterozygosity
Cell Cycle Proteins
Adenocarcinoma
Biology
medicine.disease_cause
Loss of heterozygosity
medicine
Humans
Genes, Tumor Suppressor
Esophagus
Mutation
Esophageal disease
F-Box Proteins
Cancer
Chromosome
General Medicine
medicine.disease
DNA-Binding Proteins
medicine.anatomical_structure
Oncology
Chromosomes, Human, Pair 4
Carcinogenesis
Gene Deletion
Transcription Factors
Subjects
Details
- ISSN :
- 14230232 and 00302414
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Oncology
- Accession number :
- edsair.doi.dedup.....79d8f4ed825de2754a746738143c9c51