Mutational and LOH Analyses of the Chromosome 4q Region in Esophageal Adenocarcinoma
Autor: | John M. Abraham, Stephen J. Meltzer, Takatsugu Kan, Bogdan C. Paun, Yuriko Mori, Kun Cai, Fumiaki Sato, Andreea Olaru, Anca Sterian, Agnes T. Berki, Karsten Schulmann, Suna Wang, James P. Hamilton |
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Rok vydání: | 2006 |
Předmět: |
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 |
Zdroj: | Oncology. 70:168-172 |
ISSN: | 1423-0232 0030-2414 |
DOI: | 10.1159/000094444 |
Popis: | 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. |
Databáze: | OpenAIRE |
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