Molecular Genetic Study of Human Esophageal Carcinoma
Abstract
Esophageal carcinoma is one of the most common human malignancies in certain areas of the world. Various etiological factors have been implicated in this disease, but little is known about the molecular genetic changes which accompany tumorigenesis. Two classes of genes, oncogene and tumor suppressor gene, have demonstrated susceptibility to mutations in different types of neoplasia. In the present investigation, two approaches were undertaken in the search for such genes which might be mutated during the development of esophageal carcinoma. In the first, the human HER2 oncogene, encoding a tyrosine kinase type receptor, was identified in a transformed NIH3T3 cell line induced by one esophageal tumor DNA sample. Increased expression of multiple copies of this gene together with rearrangement at the flanking sequences was acquired during the transfection process. Analysis of the complete cDNA sequence of this HER2 revealed a single nucleotide difference in codon 655 within the transmembrane region compared with a published normal cDNA sequence. This difference was demonstrated to be a polymorphism by allele-specific oligonucleotide hybridization on 47 DNA samples. In addition, human sequences other than HER2 were detected in the same transformant with multiple copies and rearrangement obtained in the transfection. These results suggest that the transformation may have been achieved from overproduction of HER2 due to amplification and/or rearrangement at the flanking sequence during the experimental manipulation. The activation of HER2 gene in this assay may thus be a fortuitous event. In the second approach, the tumor suppressor gene p53 was analyzed in 18 esophageal tumor samples from Linxian, China. p53 gene spanning codon 126 through 330 was amplified by polymerase chain reaction and was sequenced directly. Seven cases (39%) bore a point mutation in the coding region of the p53 gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 16, 1991
- Accession Number
- AD1011088
Entities
People
- Zhi-qiang Zou
Organizations
- Uniformed Services University of the Health Sciences